National Cancer Institute®
Last Modified: January 1, 2002
UI - 11406530
AU - Paggi MG; Giordano A
TI - Who is the boss in the retinoblastoma family? The point of view of Rb2/p130, the little brother.
SO - Cancer Res 2001 Jun 15;61(12):4651-4
AD - Laboratory of Cell Metabolism and Pharmacokinetics, Center for Experimental Research, Regina Elena Cancer Institute, 00158 Rome, Italy. email@example.com
This review portrays an updated overview about the possible tumor suppressive properties of the Rb2/p130 gene, the third member of the retinoblastoma (RB) family of genes, including RB itself and p107. After a brief analysis of the established structural and functional similarities among the three genes, the main purpose is to critically analyze present evidence whether Rb2/p130 shares the role of a tumor suppressor. Taking into account the well-proven growth suppressive properties of Rb2/p130 and p107, we discuss the analysis of mutated or deleted forms of Rb2/p130 found in a number of human cancers. Finally, we take into consideration the data provided by the targeted disruption of each RB family gene, alone or in combination, in the mouse model.
UI - 11447760
AU - Morris EJ; Dyson NJ
TI - Retinoblastoma protein partners.
SO - Adv Cancer Res 2001;82():1-54
AD - Laboratory of Molecular Oncology, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA.
Studies of the retinoblastoma gene (Rb) have shown that its protein product (pRb) acts to restrict cell proliferation, inhibit apoptosis, and promote cell differentiation. The frequent mutation of the Rb gene, and the functional inactivation of pRb in tumor cells, have spurred interest in the mechanism of pRb action. Recently, much attention has focused on pRb's role in the regulation of the E2F transcription factor. However, biochemical studies have suggested that E2F is only one of many pRb-targets and, to date, at least 110 cellular proteins have been reported to associate with pRb. The plethora of pRb-binding proteins raises several important questions. How many functions does pRb possess, which of these functions are important for development, and which contribute to tumor suppression? The goal of this review is to summarize the current literature of pRb-associated proteins.
UI - 11584300
AU - Sherr CJ
TI - The INK4a/ARF network in tumour suppression.
SO - Nat Rev Mol Cell Biol 2001 Oct;2(10):731-7
AD - Department of Tumor Cell Biology, Howard Hughes Medical Institute, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA. firstname.lastname@example.org
The retinoblastoma protein (RB) and p53 transcription factor are regulated by two distinct proteins that are encoded by the INK4a/ARF locus. Genes encoding these four tumour suppressors are disabled, either in whole or in part, in most human cancers. A complex signalling network that interconnects the activities of RB and p53 monitors oncogenic stimuli to provide a cell-autonomous mode of tumour surveillance.
UI - 11704837
AU - Robinson GW; Wagner KU; Hennighausen L
TI - Functional mammary gland development and oncogene-induced tumor formation are not affected by the absence of the retinoblastoma gene.
SO - Oncogene 2001 Oct 25;20(48):7115-9
AD - Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, MD 20892, USA. email@example.com
Loss of cell cycle regulation in mammary epithelium results in impaired mammary gland development and neoplasia. We investigated the consequences of the absence of pRb in mammary epithelial cells during normal development and in mice that express an oncogene in the mammary epithelium. Since pRb-deficiency results in embryonic lethality, we transplanted pRb-null mammary anlagen into wild hosts. pRb-deficient mammary epithelia were capable of functional differentiation in term animals and they regenerated a differentiated gland even after multiple pregnancies. In serial transplantations no significant differences were found in outgrowth of pRb-deficient and wild type epithelia indicating that the absence of pRb does not lead to transformation. Likewise the effect of a TGFbeta1 transgene was not altered in the absence of pRb. The susceptibility of mammary epithelium to form tumors was assessed in three different models. No differences in tumor incidence were found between wild type and Rb +/- WAP-int3, MMTV-PyMT transgenic and Brcal-/- epithelia. These results demonstrate that the absence of pRb does not affect normal mammary gland development and tumorigenesis in three different mouse models investigated and suggest that loss of more than one member of the pRb pathway is required to induce mammary tumors.
UI - 11676855
AU - Sakajiri S; Kawamata N; Egashira M; Mori K; Oshimi K
TI - Molecular analysis of tumor suppressor genes, Rb, p53, p16INK4A, p15INK4B and p14ARF in natural killer cell neoplasms.
SO - Jpn J Cancer Res 2001 Oct;92(10):1048-56
AD - Division of Hematology, Department of Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421.
Natural killer (NK) cell neoplasms, which are derived from mature or precursor NK cells, are rare diseases and are observed predominantly in Asian countries. We analyzed the status of the Rb, p53, p15INK4B, p16INK4A and p14ARF genes in these diseases by Southern blot, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and western blot analysis. We used 31 NK cell neoplasms, including four cell lines derived from NK cell neoplasms, 3 myeloid / NK cell precursor acute leukemias, 4 blastic NK cell lymphoma / leukemias, 4 aggressive NK cell leukemia / lymphomas, 4 nasal NK cell lymphomas, and 12 chronic NK lymphocytosis. We found gene amplification of the p53 gene in one nasal NK cell lymphoma, and point mutations of the p53 gene in one blastic NK cell lymphoma / leukemia and one chronic NK lymphocytosis. In addition, homozygous deletions of p15, p16 and p14 genes in 5 out of 31 samples were detected; 3 were from nasal NK cell lymphoma and 2 from blastic NK cell lymphoma / leukemia. Also hemizygous deletion of the Rb gene in one blastic NK cell lymphoma was detected. Rb proteins were highly expressed in one cell line as well as two myeloid / NK cell precursor acute leukemias. In other cell lines, complete loss and an aberrant migration pattern of Rb protein expression were observed. Comparative genomic hybridization suggested that the homozygous deletions of the p15, p16 and p14 were subtle chromosomal deletions and could not be identified by standard karyotyping in some cases. Although the number of cases we analyzed was not large, alterations identified in the Rb, p53, p16, p15 and p14 genes are of significance and might be associated with tumorigenesis in NK cell neoplasms.
UI - 11781822
AU - Lefevre SH; Vogt N; Dutrillaux AM; Chauveinc L; Stoppa-Lyonnet D; Doz F;
TI - Desjardins L; Dutrillaux B; Chevillard S; Malfoy B Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma.
SO - Oncogene 2001 Dec 6;20(56):8092-9
AD - Institut Curie - CNRS UMR 147, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.
UI - 8400245
AU - Juliusson G; Gahrton G; Einhorn S; Liu Y; Oscier DG; Chapman R
TI - Chromosome abnormalities and RB1 gene deletions in chronic lymphocytic leukemia.
SO - Blood 1993 Sep 15;82(6):1938-9
UI - 8279785
AU - Klijn JG; Berns PM; Bontenbal M; Foekens JA
TI - Growth factors. Clinical implications in breast cancer.
SO - Ann N Y Acad Sci 1993 Nov 30;698():85-101
AD - Department of Medical Oncology, Rotterdam Cancer Institute, The Netherlands.
UI - 2562179
AU - Hastie ND; Bickmore W; Pritchard-Jones K; Porteous DJ; van Heyningen V
TI - Wilms tumour: a developmental anomaly.
SO - Princess Takamatsu Symp 1989;20():145-50
AD - MRC Human Genetics Unit, Western General Hospital, Edinburgh, U.K.
Wilms tumour (WT) is a developmental anomaly of the kidney which results from loss of function of at least one so called tumour suppressor gene on chromosome 11. The position of the gene at chromosome 11p13 is known through the association of WT with aniridia (lack of an iris), mental retardation and genitourinary abnormalities in the WAGR syndrome. Here we discuss the high resolution mapping studies to locate the position of the gene and conclude that the gonadal abnormalities in WAGR patients may be due to a defect in the WT gene itself. In support of this role in genitourinary development we show that a candidate WT gene is expressed in specific regions of the developing kidney and in fetal and embryonic gonads.
UI - 8071962
AU - Cowell JK; Jaju R; Kempski H
TI - Isolation and characterisation of a panel of cosmids which allows unequivocal identification of chromosome deletions involving the RB1 gene using fluorescence in situ hybridisation.
SO - J Med Genet 1994 Apr;31(4):334-7
AD - ICRF Oncology Group, Institute of Child Health, London, UK.
A series of cosmids covering the majority of the RB1 gene have been isolated from a flow sorted human chromosome 13 specific library. Using fluorescence in situ hybridisation these cosmids were all shown to hybridise to the 13q14 region but not to chromosomes known to carry subband deletions involving the RB1 gene. This panel of cosmids, therefore, can be used objectively for identification of RB1 gene deletions in tumour and normal cells.
UI - 7646764
AU - Edington KG; Loughran OP; Berry IJ; Parkinson EK
TI - Cellular immortality: a late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss.
SO - Mol Carcinog 1995 Aug;13(4):254-65
AD - Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow, Scotland.
Many human tumors contain variant cells that, unlike their normal counterparts, possess indefinite proliferative potential in vitro. However, little is known of the relevance of these immortal cells to human carcinomas in vivo. To investigate immortality in a human tumor system, we established cultures from different stages of head and neck squamous carcinoma (SCC-HN). All the neoplastic cultures were transformed because they showed very low cornification in surface or suspension culture and were partially or completely resistant to suspension-induced death. Immortal variants were not detected in premalignant erythroplakia cultures, but their frequency increased with tumor progression, indicating that immortality is a late event in carcinogenesis. Some late-stage carcinomas still produced senescent cultures, but, significantly, all recurrent tumors were immortal. Immortal but not senescent carcinoma cultures were associated with p53 dysfunction and a high frequency of allele loss, indicative of tumor suppressor gene inactivation. These results show that there are at least two classes of human SCC-HN that are phenotypically and genotypically distinct and that the pathological stage of a given tumor is not necessarily indicative of the kind of cells it contains.
UI - 7475269
AU - Arif M; Tanaka K; Asou H; Ohno R; Kamada N
TI - Independent clones of trisomy 12 and retinoblastoma gene deletion in Japanese B cell chronic lymphocytic leukemia, detected by fluorescence in situ hybridization.
SO - Leukemia 1995 Nov;9(11):1822-7
AD - Department of Cancer Cytogenetics, Hiroshima University, Japan.
Trisomy 12 and a deletion of chromosome 13 are the most common chromosome abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL). We determined the frequencies of these abnormalities in Japanese B-CLL patients by FISH in interphase nuclei. Specimens from 42 patients were analyzed using both DNA probes specific to the centromeric region of chromosome 12 and the retinoblastoma (RB) gene. Among 42 patients, eight had trisomy 12 and 12 had the RB gene deletion. We found aberrations of trisomy 12 and the RB gene deletion in a totally different group of patients. This suggested that the trisomy 12 and the RB gene deletion occur in different clones and the presence of which in the same patient may be rare. Furthermore, the frequency of trisomy 12 (19%) found in Japanese B-CLL was lower than that in Western countries (30-35%). On the contrary, the frequency of the RB gene deletion (28.6%) was almost the same as in European B-CLL (30-35%). These results will be helpful in understanding the leukemogenesis of B-CLL.
UI - 8528059
AU - Zandecki M; Facon T; Preudhomme C; Vanrumbeke M; Vachee A; Quesnel B;
TI - Lai JL; Cosson A; Fenaux P The retinoblastoma gene (RB-1) status in multiple myeloma: a report on 35 cases.
SO - Leuk Lymphoma 1995 Aug;18(5-6):497-503
AD - Laboratoire d'Hematologie, A, C.H.U. Lille, France.
We looked for abnormalities of the retinoblastoma (RB-1) gene and of RB protein expression in 35 patients with multiple myeloma (MM). Mutations in exons 20 to 24 of the RB-1 gene (exons where mutations predominate in retinoblastoma and other solid tumors) were analyzed by single stranded conformation polymorphism (SSCP). RB-1 protein was studied in bone marrow plasma cells by immunocytochemistry (ABC peroxidase technique) with a specific monoclonal antibody. Southern blot analysis of RB-1 gene was also performed in 20 of the patients. Twenty two patients analyzed had advanced disease (stage III or, in one case, plasma cell leukemia) and cytogenetic analysis (performed in 31 cases) found monosomy 13 in 9 patients. No rearrangement of the RB-1 gene was found by Southern analysis. Absent or greatly reduced RB-1 protein level was found in plasma cells in 4 of the patients (11%), whereas normal levels were seen in the remaining cases. No point mutation in exons 20 to 24 and their flanking introns were found in any of the 35 patients. Three of the 4 patients with absent or reduced RB-1 protein expression had advanced MM (stage III: 2 cases; plasma cell leukemia: 1 case); all 4 patients were resistant to treatment (as compared to 7 of the 31 patients with normal RB-1 protein levels); only one of them was subsequently found to have monosomy 13 (as compared to 9 of the 28 other karyotyped patients). Our findings suggest that abnormalities of the RB-1 gene and its expression are rare in MM. Absent or reduced expression of RB-1 protein was not significantly correlated to monosomy 13 and was not associated with gross rearrangements of the RB-1 gene by Southern analysis or point mutations in exons 20 to 24 of the gene. Reduced expression of RB-1 protein may be associated with advanced disease and poor response to treatment, although larger numbers of patients will be required for more adequate conclusions.
UI - 8866236
AU - Belchis DA; Meece CA; Benko FA; Rogan PK; Williams RA; Gocke CD
TI - Loss of heterozygosity and microsatellite instability at the retinoblastoma locus in osteosarcomas.
SO - Diagn Mol Pathol 1996 Sep;5(3):214-9
AD - Department of Pathology, Penn State University College of Medicine, Hershey, USA.
Studies of osteosarcoma cell lines or frozen tissue have detected loss of heterozygosity (LOH) at the retinoblastoma (RB) locus by Southern blot analysis or restriction fragment length polymorphism. Most archived clinical specimens cannot be analyzed by these techniques. We analyzed formalin-fixed, paraffin-embedded samples from 19 cases of osteosarcoma for molecular changes at the RB locus using polymerase chain reaction amplification of polymorphic short tandem repeat sequences (microsatellite repeats). Four repeat sequences, two within and two flanking the RB gene, were analyzed. Fourteen of 18 informative cases (78%) showed molecular changes at the RB locus. LOH was identified in 13 cases (72%). Unexpectedly, microsatellite instability (MI) was found in eight cases (44%). All of the cases of MI involved alterations of more than one repeat unit, and six of eight were associated with LOH. LOH was identified at three unlinked loci in one case and at a single locus in another Microsatellite analysis of archival tissue yields prevalence rates of LOH comparable to those found by other methods and has the added advantage of showing MI. The ability to use formalin-fixed, paraffin-embedded tissue extends genetic analysis to routinely processed surgical material and may permit molecular confirmation of challenging cases of osteosarcoma.
UI - 9209389
AU - Hirai H; Ogawa S; Hangaishi A; Takahashi T; Kurokawa M; Mitani K; Ueda
TI - R; Yazaki Y Recent progress in molecular mechanisms of leukemogenesis: the cyclin-dependent kinase 4-inhibitor gene in human leukemias.
SO - Leukemia 1997 Apr;11 Suppl 3():358-60
AD - Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
In order to clarify the significance of p16 gene (CDKN2) inactivation and its disease specificity among hematopoietic tumors, configurations of the p16 gene as well as those of the adjacent p15 and interferon alpha (IFN alpha) genes were examined in primary hematopoietic tumors. Loss of the p16 gene is frequent in and highly specific to lymphoid tumors among hematopoietic tumors. Gene deletions but not minute mutations should be the predominant mechanism of p16 gene inactivation in these types of tumors. The p16 gene is most frequently deleted among the p16, p15 and IFN alpha genes and thus should be the target of deletions in this locus. Deletions of the p16 gene were frequently observed in tumors carrying chromosome 9p abnormalities while a significant number of cases showed loss of the p16 gene without chromosome 9p abnormalities. So far inactivation of p53 and Rb tumor suppressors have also been found in lymphoid tumors. In our study, we detected homozygous deletions of p16 gene in 20%, loss of Rb protein in 28%, and p53 gene alterations in 8% of lymphoid tumors. Notably, 44% of lymphoid tumors showed inactivation of at least one of the three tumor suppressors, suggesting these tumor suppressors are important for lymphoid tumorigenesis. Inactivations of these tumor suppressors should independently occur in development of lymphoid tumors.
UI - 11519849
AU - Suhardja A; Kovacs K; Rutka J
TI - Genetic basis of pituitary adenoma invasiveness: a review.
SO - J Neurooncol 2001 May;52(3):195-204
AD - Division of Neurosurgery, University of Toronto, Ontario, Canada.
Compatible with contemporary paradigms of the role of genetic aberrations in the progression of human tumors, the growth of pituitary tumors into a state of invasiveness appears to be due to genetic alterations. Amplification of H-ras and c-myc oncogenes and mutations of p53, nm23 and Rb genes have been identified disproportionately more in aggressive tumors and, in the case of Rb gene, in pituitary carcinomas, providing evidence that amplification of these oncogenes (H-ras and c-myc) and inactivation of tumor suppressor genes (p53, nm23 and Rb) seem to be at least one mechanism by which pituitary tumors progress. The current level of management of invasive pituitary adenomas should become more comprehensive as the advances in our understanding of genetic basis of pituitary adenoma invasiveness becomes translated into development of novel chemotherapy or gene transfer technique.
UI - 11414476
AU - Alexander JM
TI - Tumor suppressor loss in pituitary tumors.
SO - Brain Pathol 2001 Jul;11(3):342-55
AD - Harvard Medical School, Boston, MA, USA. firstname.lastname@example.org
The current model of human neoplasia invokes a number of potential genomic alterations that impact cellular phenotype and proliferative rates. In the majority of human tumor models, the transformation from normal cells to neoplastic lesion is a multistep process. This review offers a specific overview of the involvement of tumor suppressor genes (TSGs) in the pathogenesis of human pituitary adenomas. TSG genetic lesions, such as BRCA1 in breast cancer and p53 in Li-Fraumeni Syndrome, have been identified in both sporadic and heritable human endocrine tumors. Familial neoplastic syndromes like multiple endocrine neoplasia type 1 (MEN1) that include pituitary tumor formation as part of a broad clinical spectrum of disease represent a unique opportunity to investigate the general mechanisms of tumorigenesis, and well as genes responsible for sporadic endocrine tumors. Similarly, homologous recombination knockout mice with selectively ablated candidate TSGs have also shed light on the molecular mechanisms of pituitary cell proliferation and tumor suppression. However, despite insights into pituitary tumorigenesis generated by heritable neoplasia syndromes and mouse knockout of critical TSGs that display a pituitary tumor phenotype, the molecular pathogenesis of human pituitary adenomas remains largely an enigma. Thus, the role of TSGs, if any, in sporadic pituitary adenoma formation has yet to be determined, despite our greater understanding of the molecular mechanisms underlying pituitary cell function and phenotype.
UI - 11761929
AU - Nishida N; Fukuda Y
TI - [Tumor suppressor RB gene and its related molecules in hepatocellular carcinoma]
SO - Nippon Rinsho 2001 Oct;59 Suppl 6():134-7
AD - Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.