Table of Contents
1
UI - 11569231
AU - Medvedev VL
TI -
[Hormone-resistant epithelial cancer of the prostate]
SO - Urologiia 2001 Jul-Aug;(4):29-33
The study of the prognostic criteria of hormone-resistant prostatic
cancer (PC) by specifying expression of androgen receptor protein as
well as Bcl-2 and p53 proteins, apoptosis regulators, has demonstrated
that tumor cells of hormone-sensitive and hormone-resistant PC forms
have different variants of immunophenotype. Hormone-resistance is
typical for tumors from urothelial, basal and neuroendocrine PC cells,
glandular epithelium cells which lost androgen receptors (AR) and tumors
consisting of cells which retain AR but simultaneously express Bcl-2
and/or p53 genes. The discovery of androgen-resistant cancer from
glandular epithelium which has immunophenotype characteristics of a
hormone-dependent tumor indicates the existence of other mechanisms of
protection against apoptosis. The development of hormone-resistant
cancer 2.5-3 years after hormonal therapy is associated with changes in
immunophenotype of tumor cells. They become Bcl-2- and/or p53-positive
while part of them lose AR. Thus, immunophenotype of tumor cells may
serve a prognostic marker of hormonal resistance of the tumor and
dictate the treatment policy.
2
UI - 11774033
AU - Maliner-Stratton MS; Klein RD; Udayakumar TS; Nagle RB; Bowden GT
TI -
Interleukin-1beta-induced promatrilysin expression is mediated by
NFkappaB-regulated synthesis of interleukin-6 in the prostate carcinoma
cell line, LNCaP.
SO - Neoplasia 2001 Nov-Dec;3(6):509-20
AD - Department of Radiation Oncology, University of Arizona Health Sciences
Center, Tucson, AZ 85724, USA. msuzannestratton@aol.com
Previously, our laboratory showed that interleukin-1beta (IL-1beta)
secreted by lipopolysaccharide-activated monocytes induces promatrilysin
expression in the prostate carcinoma cell line, LNCaP. We now
demonstrate that IL-1beta-induced promatrilysin expression is mediated
by an indirect mechanism that requires nuclear factor Kappa B
(NFkappaB)-dependent synthesis of IL-6. Inhibition of protein synthesis
with cycloheximide blocked IL-1beta-mediated induction of matrilysin
mRNA suggesting that synthesis of one or more additional factors is
required for IL-1beta-induced promatrilysin protein expression. Blockage
of NFkappaB transactivation activity abrogated IL-1beta-induced
promatrilysin expression to baseline levels suggesting that NFkappaB
transactivation activity is necessary. Inhibition of IL-6 activity
attenuated IL-1beta-induced promatrilysin, but not NFkappaB
transactivation activity indicating that IL-6 acts downstream of
NFkappaB in potentiation of IL-1beta-mediated promatrilysin expression.
Inhibition of protein synthesis with cycloheximide did not alter
IL-6-induced induction of matrilysin mRNA indicating that, contrary to
the mechanism by which IL-1beta regulates promatrilysin expression,
IL-6-mediated matrilysin mRNA expression does not require new protein
synthesis. Transient transfection with dominant negative STAT3 inhibited
IL-1beta- and IL-6-induced promatrilysin. These data provide evidence
that NFkappaB-mediated IL-6 synthesis is required for IL-1beta-induced
promatrilysin expression, and IL-6 signaling through STAT3 plays a role
in IL-1beta-induced promatrilysin expression.
3
UI - 11839815
AU - Abdulkadir SA; Magee JA; Peters TJ; Kaleem Z; Naughton CK; Humphrey PA;
TI -
Milbrandt J
Conditional loss of Nkx3.1 in adult mice induces prostatic
intraepithelial neoplasia.
SO - Mol Cell Biol 2002 Mar;22(5):1495-503
AD - Department of Pathology, University of Alabama at Birmingham School of
Medicine, Birmingham, Alabama 35294, USA. sabdulka@path.uab.edu
The homeodomain-containing transcription factor NKX3.1 is a putative
prostate tumor suppressor that is expressed in a largely
prostate-specific and androgen-regulated manner. Loss of NKX3.1 protein
expression is common in human prostate carcinomas and prostatic
intraepithelial neoplasia (PIN) lesions and correlates with tumor
progression. Disruption of the murine Nkx3.1 gene results in defects in
prostate branching morphogenesis, secretions, and growth. To more
closely mimic the pattern of NKX3.1 loss that occurs in human prostate
tumors, we have used Cre- and loxP-mediated recombination to delete the
Nkx3.1 gene in the prostates of adult transgenic mice. Conditional
deletion of one or both alleles of Nkx3.1 leads to the development of
preinvasive lesions that resemble PIN. The pattern of expression of
several biomarkers (Ki-67, E-cadherin, and high-molecular-weight
cytokeratins) in these PIN lesions resembled that observed in human
cases of PIN. Furthermore, PIN foci in mice with conditional deletion of
a single Nkx3.1 allele lose expression of the wild-type allele. Our
results support the role of NKX3.1 as a prostate tumor suppressor and
indicate a role for this gene in tumor initiation.
4
UI - 11584064
AU - Lynch HT; Sanger WG; Pirruccello S; Quinn-Laquer B; Weisenburger DD
TI -
Familial multiple myeloma: a family study and review of the literature.
SO - J Natl Cancer Inst 2001 Oct 3;93(19):1479-83
AD - Department of Preventive Medicine, Creighton University School of
Medicine, Omaha, NE 68178, USA. htlynch@creighton.edu
BACKGROUND: The etiology of multiple myeloma (MM) remains obscure,
although reports of familial clustering have implicated both a host
susceptibility factor and environmental effects. Here we describe the
medical histories of members of a family prone to MM. METHODS: We
developed a pedigree for an MM-prone family by using information
obtained from a questionnaire. Protein immunoelectrophoresis of serum
and urine from the proband and from 19 family members was performed to
detect monoclonal immunoproteins. Peripheral blood obtained from the
proband and from five relatives was subjected to standard cytogenetic
studies to detect constitutional chromosomal abnormalities.
Multifluor-fluorescence in situ hybridization (M-FISH) and standard FISH
studies were performed on peripheral blood from the proband and from two
other affected living relatives to determine their karyotypes and to
detect clonal chromosomal abnormalities frequently seen in patients with
MM. RESULTS: Within this family, a sibship of seven included three
individuals (including the proband) with histologically verified MM and
two individuals with a monoclonal gammopathy of unknown significance
(MGUS), as determined by immunoelectrophoresis of serum and urine. This
family also had members with acute lymphocytic leukemia, malignant
melanoma, and prostate cancer. In the family members tested, we detected
no constitutional chromosomal abnormality. None of the three individuals
analyzed by FISH had a deletion of the retinoblastoma (Rb-1) locus,
which is frequently deleted in patients with MM, and only one (the
proband) had a translocation involving chromosomes 11 and 14, a clonal
abnormality commonly seen in MM. CONCLUSION: The study of familial MM
may provide insights into the pathogenesis and, ultimately, the control
and prevention of MM and related disorders.
5
UI - 11720249
AU - Panz VR; Joffe BI; Spitz I; Lindenberg T; Farkas A; Haffejee M
TI -
Tandem CAG repeats of the androgen receptor gene and prostate cancer
risk in black and white men.
SO - Endocrine 2001 Jul;15(2):213-6
AD - Department of Medicine, University of the Witwatersrand, Johannesburg,
South Africa. 014panz@chiron.wits.ac.za
The most common malignancy in men worldwide is cancer of the prostate.
Androgens play a direct role in normal and malignant growth of prostate
cells via the androgen receptor (AR). This study analyzed the
polymorphic CAG repeat sequence in exon 1 of the AR gene to determine if
the number of repeats might be an indicator of prostate cancer risk or
aggressive disease. DNA was extracted from blood samples of 20 black and
20 white men with well-documented prostate cancer and 40 healthy
controls (20 blacks and 20 whites). PCR amplification was followed by
gel electrophoresis and DNA sequencing. This region normally contains
between 9 and 29 repeats. Patients and controls both had minor
variations in the number of repeats, which ranged from 13 to 27 with 21
being the most frequent allele. Black controls and patients both had a
mean of 20 +/- 3 repeats; in whites the mean was significantly lower in
patients than controls (21 +/- 2 versus 23 +/- 2; p = 0.004). Combined
black and white patients also had a lower number than the combined group
of controls (20 +/- 3 versus 22 +/- 3; p = 0.02). Similarly, black and
white patients with aggressive disease had a lower number than patients
whose disease was more slowly progressive (19 +/- 2 versus 22 +/- 3; p =
0.02). We conclude that the small differences in the number of CAG
repeats in both black and white patients do not appear to be a strong
indicator of risk or aggressive disease but that this size polymorphism
may be one of many genetic and environmental risk factors involved in
prostate cancer.
6
UI - 11818495
AU - Schmitt JF; Millar DS; Pedersen JS; Clark SL; Venter DJ; Frydenberg M;
TI -
Molloy PL; Risbridger GP
Hypermethylation of the inhibin alpha-subunit gene in prostate
carcinoma.
SO - Mol Endocrinol 2002 Feb;16(2):213-20
AD - Monash Institute of Reproduction and Development, Monash University,
Clayton, Victoria 3168, Australia.
Inhibin is composed of an alpha- and a beta-subunit. Transgenic studies
assigned a tumor-suppressive role to the inhibin alpha-subunit, and in
human prostate cancer inhibin alpha-subunit gene expression was
down-regulated. This study examined the inhibin alpha-subunit gene
promoter and gene locus to determine whether promoter hypermethylation
or LOH occurred in DNA from prostate cancer. The 5'-untranslated region
of the human inhibin alpha-subunit gene was sequenced and shown to be
highly homologous to the bovine, rat, and mouse inhibin alpha-subunit
promoter sequences. A 135-bp region of the human promoter sequence that
continued a cluster of CpG sites was analyzed for hypermethylation.
Significant (P < 0.001) hypermethylation of the inhibin alpha-subunit
gene promoter occurred in DNA from Gleason pattern 3, 4, and 5
carcinomas compared with nonmalignant tissue samples. A subset of the
carcinomas with a cribriform pattern were unmethylated. LOH at 2q32-36,
the chromosomal region harboring the inhibin alpha-subunit gene, was
observed in 42% of prostate carcinomas. These data provide the first
demonstration that promoter hypermethylation and LOH are associated with
the inhibin alpha-subunit gene and gene locus in prostate cancer.
7
UI - 11888886
AU - Mousses S; Bubendorf L; Wagner U; Hostetter G; Kononen J; Cornelison R;
TI -
Goldberger N; Elkahloun AG; Willi N; Koivisto P; Ferhle W; Raffeld M;
Sauter G; Kallioniemi OP
Clinical validation of candidate genes associated with prostate cancer
progression in the CWR22 model system using tissue microarrays.
SO - Cancer Res 2002 Mar 1;62(5):1256-60
AD - Cancer Genetics Branch, National Human Genome Research Institute, NIH,
Bethesda, Maryland 20892, USA.
To explore molecular mechanisms of prostate cancer progression, we
applied tissue microarrays (TMAs) to analyze expression of candidate
gene targets discovered by cDNA microarray analysis of the CWR22
xenograft model system. A TMA with 544 clinical specimens from different
stages of disease progression was probed by mRNA in situ hybridization
and protein immunohistochemistry. There was an excellent correlation (r
= 0.96; n = 16) between the expression levels of the genes in the
xenografts by cDNA microarray and mRNA in situ hybridization on a TMA.
One of the most highly overexpressed genes in hormone-refractory CWR22R
xenografts was the S100P gene. This gene, coding for a calcium signaling
molecule implicated in the loss of senescence, was also significantly
associated with progression in clinical tumors by TMA analysis (P <
0.001), suggesting dysregulation of this pathway in hormone-refractory
and metastatic prostate cancers. Conversely, two genes that were
down-regulated during tumor progression in the CWR22 model system were
validated in vivo: crystallin mu (CRYM) and a LIM-domain protein LMO4
both showed significantly lower mRNA levels in hormone-refractory tumors
as compared with primary tumors (P < 0.001). These results illustrate a
strategy for rapid clinical validation at the mRNA and protein level of
gene targets found to be differentially expressed in cDNA microarray
experiments of model systems of cancer.
8
UI - 11693967
AU - Hsieh CL; Chung LW
TI -
New prospectives of prostate cancer gene therapy: molecular targets and
animal models.
SO - Crit Rev Eukaryot Gene Expr 2001;11(1-3):77-120
AD - Department of Urology, University of Virginia School of Medicine,
Charlottesville 22908, USA.
Prostate cancer is the most common cancer and the second leading cause
of cancer-related death among North American men. The low cure rate for
prostate cancer is associated with the fact that many patients have
metastatic disease at the time of disease presentation. Currently
available therapeutic modalities for prostate cancer, such as surgery,
radiation, hormone therapy, and chemotherapy, have failed to cure
patients because these therapies are not sufficiently tumor-specific,
resulting in dose-limiting toxicity. Therefore, gene therapy may offer
great promise in this regard. In this article, we summarize current
advances in gene therapy technologies for the treatment of cancer in
general, and future prospects for treatment of human prostate cancer
metastasis. We specifically emphasize current studies for improvement,
both in the efficiency and the specificity of viral and nonviral
vectors, and restricted transgene expression in tumors, to achieve
selective targeting with minimized host organ toxicity, based on the
molecular understanding of potential regulatory differences between
normal and tumor cells. Cell and animal models used to study prostate
cancer growth, invasion, and metastasis, and their usefulness in
preclinical evaluation of therapeutic vectors in the treatment of
prostate cancer skeletal metastasis are also discussed.
9
UI - 11870882
AU - Patra SK; Patra A; Zhao H; Dahiya R
TI -
DNA methyltransferase and demethylase in human prostate cancer.
SO - Mol Carcinog 2002 Mar;33(3):163-71
AD - Department of Urology, University of California San Francisco and
Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Recent studies have shown that cytosine-5 methylation at CpG islands in
the regulatory sequence of a gene is one of the key mechanisms of
inactivation. The enzymes responsible for CpG methylation are DNA
methyltransferase (DNMT) 1, DNMT3a, and DNMT3b, and the enzyme
responsible for demethylation is DNA demethylase (MBD2). Studies on
methylation-demethylation enzymes are lacking in human prostate cancer.
We hypothesize that MBD2 enzyme activity is repressed and that DNMT1
enzyme activity is elevated in human prostate cancer. To test this
hypothesis, we analyzed enzyme activities, mRNA, and protein levels of
MBD2 and DNMT1, DNMT3a, and DNMT3b in human prostate cancer cell lines
and tissues. The enzyme activities of DNMTs and MBD2 were analyzed by
biochemical assay. The mRNA expression was analyzed by reverse
transcriptase-polymerase chain reaction and by Northern blotting. The
protein expression was measured by immunohistochemistry with specific
antibodies. The results of these experiments demonstrated that (1) the
activity of DNMTs was twofold to threefold higher in cancer cell lines
and cancer tissues, as compared with a benign prostate epithelium cell
line (BPH-1) and benign prostatic hyperplasia (BPH) tissues; (2) MBD2
activity was lacking in prostate cancer cell lines but present in BPH-1
cells; (3) immunohistochemical analyses exhibited higher expression of
DNMT1 in all prostate cancer cell lines and cancer tissues, as compared
with BPH-1 cell lines and BPH tissues; (4) MBD2 protein expression was
significantly higher in BPH-1 cells and lacking in prostate cancer cell
lines and, in BPH tissues, MBD2 protein expression was poorly observed,
as compared with no expression in prostate cancer tissues; and (5) mRNA
expression for DNMT1 was upregulated in prostate cancer, as compared
with BPH-1, and mRNA expression for MBD2 was found to be significantly
expressed in all cases. The results of these studies clearly demonstrate
that DNMT1 activity is upregulated, whereas MBD2 is repressed at the
level of translation in human prostate cancer. These results may
demonstrate molecular mechanisms of CpG hypermethylation of various
genes in prostate cancer. Copyright 2002 Wiley-Liss, Inc.
10
UI - 11901478
AU - Cooper CR; Chay CH; Pienta KJ
TI -
New discoveries in prostate cancer biology and treatment. 5-9 December
2001, Naples, Florida, USA.
SO - Expert Opin Ther Targets 2002 Feb;6(1):123-7
AD - University of Michigan Comprehensive Cancer Center, Department of
Internal Medicine, Division of Haematology/Oncology and Department of
Urology, Ann Arbor, MI 48109, USA.
Androgen independence and bone metastasis are lethal complications in
patients with advanced prostate cancer. Presently, there is no cure for
patients with androgen-independent prostate cancer. In order to develop
more effective therapies for this disease, the molecular events involved
in the development of androgen independence and bone metastasis must be
elucidated and then targeted by therapeutic agents. Several studies
presented at a recent conference on prostate cancer sponsored by the
American Association for Cancer Research (AACR) provided evidence that
prostate cancer metastasis to bone is mediated by the prostate cancer
cell expression of molecules that allow the cells to invade, grow in and
stimulate cells in the bone microenvironment resulting in an
osteoblastic reaction. Androgen independence was reportedly mediated by
an increased expression of survival genes following androgen ablation
therapies and several molecular mechanisms involved in genetic
instability. Treatment strategies are being designed to target some of
the molecular events involved in androgen independence and bone
metastasis. Targeting these molecular events with combinational
therapies will hopefully delay the progression to androgen independence
in patients with early stage disease, suppress the growth of
androgen-independent cells in patients with advanced disease and enhance
the chemosensitivity of androgen-independent cells.
11
UI - 11880592
AU - Lamartiniere CA; Cotroneo MS; Fritz WA; Wang J; Mentor-Marcel R;
TI -
Elgavish A
Genistein chemoprevention: timing and mechanisms of action in murine
mammary and prostate.
SO - J Nutr 2002 Mar;132(3):552S-558S
AD - Department of Pharmacology and Toxicology, University of Alabama at
Birmingham Comprehensive Cancer Center, Birmingham, AL 35294, USA.
coral.lamartiniere@ccc.uab.edu
We investigated the potential of genistein, the primary isoflavone of
soy, to protect against breast and prostate cancers in animal models.
For mammary cancer studies, Sprague-Dawley rats were fed AIN-76A diet
plus minus 250 mg genistein/kg diet. Dimethylbenz[a]anthracene was
administered by gavage at d 50 postpartum to induce mammary tumors.
Mammary cancer chemoprevention was demonstrated after prepubertal and
combined prepubertal and adult genistein treatments but not after
prenatal- or adult-only treatments, demonstrating that the timing of
exposure to genistein is important for mammary cancer chemoprevention.
The cellular mechanism of action was found to be mammary gland and cell
differentiation, as shown by whole-mount analysis and beta-casein
expression. An imprinting effect was shown for epidermal growth factor
receptor expression in mammary terminal end buds. For prostate cancer
studies, we used two models. The first was a chemically
(N-methylnitrosourea) induced prostate cancer rat model. Genistein in
the diet inhibited the development of invasive adenocarcinomas in a
dose-dependent manner. The second model was a transgenic mouse model
that resulted in spontaneously developing adenocarcinoma tumor of the
prostate. Genistein in the diet reduced the incidence of poorly
differentiated prostatic adenocarcinomas in a dose-dependent manner and
down-regulated androgen receptor, estrogen receptor-alpha, progesterone
receptor, epidermal growth factor receptor, insulin-like growth
factor-I, and extracellular signal-regulated kinase-1 but not estrogen
receptor-beta and transforming growth factor-alpha mRNA expressions. We
conclude that dietary genistein protects against mammary and prostate
cancers by regulating specific sex steroid receptors and growth factor
signaling pathways.
12
UI - 11920501
AU - Meyer-Siegler KL; Bellino MA; Tannenbaum M
TI -
Macrophage migration inhibitory factor evaluation compared with prostate
specific antigen as a biomarker in patients with prostate carcinoma.
SO - Cancer 2002 Mar 1;94(5):1449-56
AD - Research and Development, Bay Pines Veterans Administration Medical
Center, Bay Pines, Florida 33744, USA. ksiegler@hsc.usf.edu
BACKGROUND: Cytokines are polypeptides that constitute a class of
chemical mediator molecules that modulate cell growth by inducing
specific target gene expression. The objective of this study was to
evaluate the clinical usefulness of serum evaluation of the cytokine
macrophage migration inhibitory factor (MIF) in patients undergoing
routine prostate specific antigen (PSA) screening. METHODS: In this
preliminary, retrospective study, the authors report the development of
an enzyme-linked immunosorbent assay (ELISA) for MIF determination in
serum samples. A polymerase chain reaction (PCR)-based assay
investigated associations between MIF expression and prostate carcinoma
(CaP). The authors developed a relative quantitative reverse
transcriptase-PCR assay to determine MIF mRNA amounts within
laser-capture microscopy (LCM)-dissected prostate epithelial cells.
RESULTS: A comparison of serum MIF levels and total PSA levels
identified a positive correlation (correlation coefficient [r2] = 0.61;
P < 0.001; n = 509 patients), suggesting an association between elevated
serum concentrations of these proteins and CaP. A correlation of serum
MIF levels with a diagnosis of CaP demonstrated that patients with a
previous CaP diagnosis had significantly elevated serum MIF
concentrations (mean +/- standard deviation, 6.8 +/- 0.87 ng/mL; P <
0.001). To associate altered serum MIF levels with MIF mRNA expression
within prostate epithelial cells, LCM-dissected prostate epithelial
cells (formalin fixed biopsies from three different patients) were used
to determine MIF mRNA amounts by PCR analysis. On average, MIF mRNA
amounts were 6.5 times higher in CaP epithelial cells that were invasive
to the margin compared with MIF mRNA amounts in normal prostate
epithelial cells within the same biopsy specimen. CONCLUSIONS: The ELISA
data from the current study suggested an association between increased
MIF expression and CaP and suggested that serum MIF concentration may
serve as a prognostic marker for CaP. Copyright 2002 American Cancer
Society.
13
UI - 11801547
AU - Kang JS; Calvo BF; Maygarden SJ; Caskey LS; Mohler JL; Ornstein DK
TI -
Dysregulation of annexin I protein expression in high-grade prostatic
intraepithelial neoplasia and prostate cancer.
SO - Clin Cancer Res 2002 Jan;8(1):117-23
AD - Department of Surgery, Divisions of Urology, University of North
Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
PURPOSE: To determine expression levels of annexin I (lipocortin I) in
patient-matched benign prostatic epithelium (BPE), high-grade prostatic
intraepithelial neoplasia (HGPIN), and prostate cancer (CaP).
EXPERIMETNAL DESIGN: Annexin I protein expression was examined with a
standard immunohistochemical protocol in 69 radical prostatectomy
specimens, 45 of which also contained HGPIN. Immunostained sections were
scored visually by a genitourinary pathologist and mean optical density
was measured with digital image analysis. Real-time fluorescence
quantitative PCR was used to measure expression levels of annexin I mRNA
in patient-matched CaP and BPE from 14 snap-frozen, radical
prostatectomy specimens. RESULTS: Annexin I protein expression was
reduced in 91% (41/45) of HGPIN lesions and 94% (65/69) of invasive CaP
compared with BPE in the same histological section when assessed
visually. Mean absorbance was reduced significantly (P < 0.05) in 97.7%
(44/45) of HGPIN lesions and 98.5% (68/69) of CaP glands compared with
BPE. In 79% of cases (11/14; P < 0.05), mRNA expression was reduced in
CaP as compared with patient-matched BPE. Annexin I mRNA and protein
expression levels did not correlate with Gleason grade, pathological
stage, or race. CONCLUSIONS: Down-regulation of annexin I protein
expression is a common finding in HGPIN and CaP, suggesting that annexin
I dysregulation may be an important early event in CaP initiation.
Because mRNA levels are reduced in a high proportion of cases, one
likely mechanism for annexin I dysregulation occurs at the level of gene
transcription. Results of these studies support a valuable role for a
molecular profiling approach to CaP research.
14
UI - 11898181
AU - Diefenbach MA; Schnoll RA; Miller SM; Brower L
TI -
Genetic testing for prostate cancer. Willingness and predictors of
interest.
SO - Cancer Pract 2000 Mar-Apr;8(2):82-6
AD - Division of Population Science, Fox Chase Cancer Center, 510 Township
Line Road, Third Floor, Cheltenham, Pennsylvania 19012, USA.
PURPOSE: As researchers come closer to identifying the genes responsible
for prostate cancer, the possibility of genetic testing for men at risk
for prostate cancer becomes more likely. This study examined the
following: 1) the degree to which men with (n = 43) or without (n = 83)
a family history of prostate cancer would be interested in genetic
testing; and 2) the degree to which interest in testing was associated
with demographic, family history, and psychosocial factors. DESCRIPTION
OF STUDY: Participants (N = 126) were accrued through patients who had
been treated for prostate cancer at Fox Chase Cancer Center (n = 39) and
through newspaper advertisements (n = 87). All participants completed a
questionnaire sent by mail. RESULTS: Seventy-four percent of men were
probably (50%) or definitely (24%) interested in testing. Participants
with a family history of prostate cancer reported that they would be
willing to pay substantially more for a genetic test compared with those
without a family history. Elevated worry about prostate cancer and
concerns about treatment-related side effects were associated with
greater interest in genetic testing. CLINICAL IMPLICATIONS: Findings
demonstrate a need for the development of genetic counseling protocols
for at-risk men who are interested in genetic testing, once this test
becomes available.
15
UI - 11901845
AU - Anonymous
TI -
Potential screening test for prostate cancer.
SO - Expert Rev Mol Diagn 2001 Nov;1(4):367-8
16
UI - 11901827
AU - Anonymous
TI -
Microscopic cantilever aids assay for prostate cancer.
SO - Expert Rev Mol Diagn 2001 Sep;1(3):247
17
UI - 11901761
AU - Ewis AA; Lee J; Naroda T; Sasahara K; Sano T; Kagawa S; Iwamoto T;
TI -
Nakahori Y
Linkage between prostate cancer incidence and different alleles of the
human Y-linked tetranucleotide polymorphism DYS19.
SO - J Med Invest 2002 Feb;49(1-2):56-60
AD - Department of Public Health, University of Tokushima, School of
Medicine, Kuramoto-cho, Tokushima 770-8503, Japan.
We studied the allele frequency distribution of the Y-chromosome linked
tetranucleotide polymorphic microsatellite locus DYS19 in 90 prostate
cancer Japanese patients from both Tokushima University hospital
(Tokushima) and Saint Marianna University hospital (Kawasaki), Japan,
comparing them to 99 matched male controls. Y-chromosomes from Japan as
well as others from different geographical regions worldwide showed the
five different alleles (A-E) with sizes varying from 186-202 bp,
respectively. Comparison between DYS19 allelic frequency distribution
among Japanese patients with prostate cancer and that of normal controls
revealed significant differences regarding susceptibility or resistance
to prostate cancer. We found that males with allele C of DYS19 are more
susceptible to develop prostate cancer than males with other alleles (p
= 0.02). The Odds Ratio was 2.04 with a 95% confidence interval
(0.75-2.42), compared with males having other alleles. In contrast,
males with the D allele of DYS19 were less exposed to prostate cancer
than other males (p = 0.002); the Odds Ratio was 0.26 with a 95%
confidence interval of (0.65-3.71). These findings support our
hypothesis that male descendants from different Y-chromosomal origins
are different regarding their susceptibility or resistance to develop
prostate cancer (as a male-specific cancer).
18
UI - 11752398
AU - Watabe T; Lin M; Ide H; Donjacour AA; Cunha GR; Witte ON; Reiter RE
TI -
Growth, regeneration, and tumorigenesis of the prostate activates the
PSCA promoter.
SO - Proc Natl Acad Sci U S A 2002 Jan 8;99(1):401-6
AD - Howard Hughes Medical Institute, University of California, Los Angeles,
CA 90095-1662, USA.
The prostate gland undergoes dramatic changes in growth status during
normal physiologic development, following androgen administration to
castrate animals, and during tumor development. The prostate stem cell
antigen (PSCA, named for its strong sequence homology to the thymocyte
marker stem cell antigen 2) is a cell surface molecule associated with
human and murine prostate cancer. To help define the regulation of this
molecule, we created a transgenic mouse strain, which uses the human
PSCA promoter region to control the expression of enhanced green
fluorescent protein (GFP). Expression of GFP was detected in
mid-gestation following the appearance of prostatic buds from the
urogenital sinus. In adult mice, GFP expression was restricted to a
subset of cells located in the distal tips of the glands. GFP expression
increased during puberty and regeneration driven by androgen and
associated with expansive growth of the prostate. GFP-positive cells
coexpressed markers associated with both basal and secretory cells in
the human prostate. Prostate carcinogenesis driven by T antigen in the
transgenic adenocarcinoma of the mouse prostate (TRAMP) model results in
an increased percentage and intensity level for PSCA promoter-driven
GFP-positive cells. This transgenic system helps define the range of
cellular changes associated with altered expression of PSCA, shows that
transcriptional control is a major component regulating PSCA levels, and
provides a useful tool to study subpopulations of prostate epithelial
cells and factors that regulate the PSCA promoter.
19
UI - 11920466
AU - Morris MJ; Reuter VE; Kelly WK; Slovin SF; Kenneson K; Verbel D; Osman
TI -
I; Scher HI
HER-2 profiling and targeting in prostate carcinoma.
SO - Cancer 2002 Feb 15;94(4):980-6
AD - Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
BACKGROUND: The clinical effects of targeting HER-2 in prostate
carcinoma are not known. This study explored the feasibility of
molecular profiling to determine the correlation between HER-2
expression, hormonal sensitivity, and the antitumor effects of
trastuzumab and paclitaxel in patients with prostate carcinoma. METHODS:
Patients with progressive androgen dependent (AD) and androgen
independent (AI) prostate carcinoma were eligible to participate in the
study. HER-2 expression was assessed on pretreatment tissue specimens,
and patients were then assigned to one of four treatment groups: AD
HER-2 positive, AD HER-2 negative, AI HER-2 positive, and AI HER-2
negative. They were treated with weekly trastuzumab at a dose of 2 mg/kg
(after a 4 mg/kg loading dose) until they experienced disease
progression, when weekly paclitaxel at 100 mg/m(2) was added. RESULTS:
The authors screened 130 patients for HER-2 expression. In total, 23
patients were treated. Six eligible patients had HER-2 positive disease;
therefore, only the AI HER-2 negative arm accrued to completion. All
patients (100%) experienced disease progression on trastuzumab alone at
or before the first 12 weeks of treatment. Fifteen patients received
combined therapy: Seven patients (47%) experienced disease progression,
5 patients (33%) had stable disease, and 3 patients (20%) had a decline
> or = 50% in prostate specific antigen PSA level or in soft tissue
disease. HER-2 overexpression was found in significant proportions only
in AI metastatic tissue samples (42% HER-2 positive; 95% confidence
interval, 14-60%). In three of nine matched pairs, the AD prostate
biopsy was HER-2 negative, and the AI metastatic sample was HER-2
positive. CONCLUSIONS: Trastuzumab is not effective as a single agent
for the treatment of patients with AI HER-2 negative tumors. HER-2
expression varies by clinical state in patients with prostate carcinoma:
Accurate HER-2 profiling requires sampling metastatic tissue in patients
with metastatic disease. Further development of trastuzumab for the
treatment of patients with metastatic prostate carcinoma is not feasible
until more reliable and practical methods of sampling metastatic disease
are developed to identify patients with HER-2 positive tumors. Copyright
2002 American Cancer Society. DOI 10.1002/cncr.10339
20
UI - 11887983
AU - Trapman J
TI -
Molecular mechanisms of prostate cancer.
SO - Eur J Cancer 2001 Oct;37 Suppl 7():S119-25
AD - Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
21
UI - 11727271
AU - Finn WG
TI -
Alternative to histologic grading of cancer.
SO - Hum Pathol 2001 Nov;32(11):1277-8
22
UI - 8759054
AU - McGarvey TW; Stearns ME
TI -
Keratinocyte growth factor and receptor mRNA expression in benign and
malignant human prostate.
SO - Exp Mol Pathol 1995 Aug;63(1):52-62
AD - Department of Pathology, Allegheny University of the Health Sciences,
Philadelphia, Pennsylvania 19102-1192, USA.
We have examined whether keratinocyte growth factor (KGF) and its
receptor are expressed in normal, fetal, and prostate cancer cells since
KGF may play a role in the growth of adenocarcinomas. In situ
hybridization studies with digoxigenin-labeled oligonucleotides
(anti-sense and sense controls) were employed to examine KGF and KGF
receptor mRNA expression in prostate cancer. We found that the KGF and
KGF receptor genes were faintly expressed in the stromal and epithelial
cells, respectively, in both fetal (n = 6) and normal adult prostate (n
= 6) tissues examined. In 10 benign prostatic hyperplasias (BPH), and in
low- and high-grade prostatic carcinoma (32 total), both the KGF gene
and the receptor mRNA were expressed in the glandular epithelial cells.
KGF was also expressed by the stromal cells in BPH and low-grade
carcinoma. Computer assisted system analysis indicated that the
intensity of epithelial labeling by both probes was increased in high
Gleason score carcinomas ( > 8) and in metastatic nodules. We interpret
the data to mean that the paracrine loop in normal prostate may be
replaced by an autocrine loop in BPH and adenocarcinomas.
23
UI - 9178898
AU - Ide H; Katoh M; Sasaki H; Yoshida T; Aoki K; Nawa Y; Osada Y; Sugimura
TI -
T; Terada M
Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB)
and its expression in prostate cancer in comparison with other BMPRs.
SO - Oncogene 1997 Mar 20;14(11):1377-82
AD - Genetics Division, National Cancer Center Research Institute, Chuo-ku,
Tokyo, Japan.
Bone metastasis is a common event in prostate cancer, and it is known
that some of the bone morphogenetic proteins (BMPs) are expressed in
prostate cancer cells, while no study on the expression of their
receptors, BMPRs, has been reported. Here we report cloning and sequence
analysis of the human BMPR-IB cDNA. We also analysed the expression of
transcripts of three types of the BMPR genes in human tissues and
prostate cancer cell lines. The BMPR-IB mRNA was present in various
organs, but the highest level was found in the prostate. Moreover, the
amount of BMPR-IB mRNA was significantly low in prostate cancer tissues
after androgen withdrawal and was also low in prostate cancer cell
lines. RT-PCR analysis showed that the BMPR-IB message was upregulated
by androgen stimulation in the LNCaP cell line which expresses the
androgen receptor. By contrast, the mRNA levels of BMPR-IA and BMPR-II
were not significantly different among non-cancerous and cancerous
prostate tissues. It was also suggested that human BMPR-IA and BMPR-IB
might have different biological functions in the prostate, although
their sequences were 85.3% identical in the serine-threonine kinase
domain.
24
UI - 10373563
AU - Abreu-Martin MT; Chari A; Palladino AA; Craft NA; Sawyers CL
TI -
Mitogen-activated protein kinase kinase kinase 1 activates androgen
receptor-dependent transcription and apoptosis in prostate cancer.
SO - Mol Cell Biol 1999 Jul;19(7):5143-54
AD - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles,
California 90095, USA.
Mitogen-activated protein (MAP) kinases phosphorylate the estrogen
receptor and activate transcription from estrogen receptor-regulated
genes. Here we examine potential interactions between the MAP kinase
cascade and androgen receptor-mediated gene regulation. Specifically, we
have studied the biological effects of mitogen-activated protein kinase
kinase kinase 1 (MEKK1) expression in prostate cancer cells. Our
findings demonstrate that expression of constitutively active MEKK1
induces apoptosis in androgen receptor-positive but not in androgen
receptor-negative prostate cancer cells. Reconstitution of the androgen
receptor signaling pathway in androgen receptor-negative prostate cancer
cells restores MEKK1-induced apoptosis. MEKK1 also stimulates the
transcriptional activity of the androgen receptor in the presence or
absence of ligand, whereas a dominant negative mutant of MEKK1 impairs
activation of the androgen receptor by androgen. These studies
demonstrate an unanticipated link between MEKK1 and hormone receptor
signaling and have implications for the molecular basis of
hormone-independent prostate cancer growth.
25
UI - 10419456
AU - Nakatani K; Thompson DA; Barthel A; Sakaue H; Liu W; Weigel RJ; Roth RA
TI -
Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and
androgen-independent prostate cancer lines.
SO - J Biol Chem 1999 Jul 30;274(31):21528-32
AD - Departments of Molecular Pharmacology, Stanford University School of
Medicine, Stanford, California 94305, USA.
We measured the insulin-stimulated amount of Akt1, Akt2, and Akt3
enzymatic activities in four breast cancer cell lines and three prostate
cancer cell lines. In the estrogen receptor-deficient breast cancer
cells and the androgen-insensitive prostate cells, the amount of Akt3
enzymatic activity was approximately 20-60-fold higher than in the cells
that were estrogen- or androgen-responsive. In contrast, the levels of
Akt1 and -2 were not increased in these cells. The increase in Akt3
enzyme activity correlated with an increase in both Akt3 mRNA and
protein. In a prostate cancer cell line lacking the tumor suppressor
PTEN (a lipid and protein phosphatase), the basal enzymatic activity of
Akt3 was constitutively elevated and represented the major active Akt in
these cells. Finally, reverse transcription-PCR was used to examine the
Akt3 expression in 27 primary breast carcinomas. The expression levels
of Akt3 were significantly higher in the estrogen receptor-negative
tumors in comparison to the estrogen receptor-positive tumors. To see if
the increase in Akt3 could be due to chromosomal abnormalities, the Akt3
gene was assigned to human chromosome 1q44 by fluorescence in situ
hybridization and radiation hybrid cell panel analyses. These results
indicate that Akt3 may contribute to the more aggressive clinical
phenotype of the estrogen receptor-negative breast cancers and
androgen-insensitive prostate carcinomas.
26
UI - 10602496
AU - Palayoor ST; Youmell MY; Calderwood SK; Coleman CN; Price BD
TI -
Constitutive activation of IkappaB kinase alpha and NF-kappaB in
prostate cancer cells is inhibited by ibuprofen.
SO - Oncogene 1999 Dec 2;18(51):7389-94
AD - Radiation Oncology Branch, National Cancer Institute, 9000 Rockville
Pike, Bethesda, Maryland, MD 20892, USA.
Apoptotic pathways controlled by the Rel/NF-kappaB family of
transcription factors may regulate the response of cells to DNA damage.
Here, we have examined the NF-kappaB status of several prostate tumor
cell lines. In the androgen-independent prostate tumor cells PC-3 and
DU-145, the DNA-binding activity of NF-kappaB was constitutively
activated and IkappaB-alpha levels were decreased. In contrast, the
androgen-sensitive prostate tumor cell line LNCaP had low levels of
NF-kappaB which were upregulated following exposure to cytokines or DNA
damage. The activity of the IkappaB-alpha kinase, IKKalpha, which
mediates NF-kappaB activation, was also measured. In PC-3 cells,
IKKalpha activity was constitutively active, whereas LNCaP cells had
minimal IKKalpha activity that was activated by cytokines. The
anti-inflammatory agent ibuprofen inhibited the constitutive activation
of NF-kappaB and IKKalpha in PC-3 and DU-145 cells, and blocked
stimulated activation of NF-kappaB in LNCaP cells. However, ibuprofen
did not directly inhibit IkappaB-alpha kinase. The results demonstrate
that NF-kappaB is constitutively activated in the hormone-insensitive
prostate tumor cell lines PC-3 and DU-145, but not in the hormone
responsive LNCaP cell line. The constitutive activation of NF-kappaB in
prostate tumor cells may increase expression of anti-apoptotic proteins,
thereby decreasing the effectiveness of anti-tumor therapy and
contributing to the development of the malignant phenotype.
27
UI - 10716737
AU - Persad S; Attwell S; Gray V; Delcommenne M; Troussard A; Sanghera J;
TI -
Dedhar S
Inhibition of integrin-linked kinase (ILK) suppresses activation of
protein kinase B/Akt and induces cell cycle arrest and apoptosis of
PTEN-mutant prostate cancer cells.
SO - Proc Natl Acad Sci U S A 2000 Mar 28;97(7):3207-12
AD - British Columbia Cancer Agency and Jack Bell Research Centre, 2660 Oak
Street, Vancouver, BC V6H 3Z6, Canada.
PTEN is a tumor suppressor gene located on chromosome 10q23 that encodes
a protein and phospholipid phosphatase. Somatic mutations of PTEN are
found in a number of human malignancies, and loss of expression, or
mutational inactivation of PTEN, leads to the constitutive activation of
protein kinase B (PKB)/Akt via enhanced phosphorylation of Thr-308 and
Ser-473. We recently have demonstrated that the integrin-linked kinase
(ILK) can phosphorylate PKB/Akt on Ser-473 in a phosphoinositide
phospholipid-dependent manner. We now demonstrate that the activity of
ILK is constitutively elevated in a serum- and anchorage-independent
manner in PTEN-mutant cells, and transfection of wild-type (WT) PTEN
into these cells inhibits ILK activity. Transfection of a
kinase-deficient, dominant-negative form of ILK or exposure to a small
molecule ILK inhibitor suppresses th
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