National Cancer Institute®
Last Modified: January 1, 2002
UI - 11191790
AU - Devilee P; Tollenaar RA; Cornelisse CJ
TI - [From gene to disease; from BRCA1 or BRCA2 to breast cancer]
SO - Ned Tijdschr Geneeskd 2000 Dec 30;144(53):2549-51
AD - Afd. Antropogenetica, Leids Universitair Medisch Centrum, Postbus 9600, 2300 RC Leiden.
Hereditary breast cancer is a heterogeneous syndrome, both phenotypically and genetically. It affects about 5% of all breast cancer patients. The presence of ovarian cancer or breast cancer in males defines important subtypes. BRCA1 and BRCA2 are involved in all hereditary breast cancer syndromes in varying degrees. Both genes confer strongly elevated breast and ovarian cancer risks in mutation carriers, but these risks may be subject to modifying effects by other factors (genetic and/or environmental) at the individual level. In the Netherlands, DNA testing is offered under the national health insurance programme and has led to the identification of over 500 families with either a BRCA1 or BRCA2 mutation. The results of the test are being used widely by Dutch women in the decision for or against prophylactic surgery.
UI - 11011299
AU - Nixon RM; Pharoah P; Tabar L; Krusemo UB; Duffy SW; Prevost TC; Chen HH
TI - Mammographic screening in women with a family history of breast cancer: some results from the Swedish two-county trial.
SO - Rev Epidemiol Sante Publique 2000 Aug;48(4):325-31
AD - MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, CB2 2SR, UK. firstname.lastname@example.org.
BACKGROUND: The objective of this study is to compare the effectiveness of mammographic screening in women with a family history of breast cancer to those without. In the invited arm of a randomised trial of breast cancer screening, data on family history of breast cancer were available on 29.179 women aged 40-74 attending for screening. Among those women, 358 were diagnosed with breast cancer during the trial. METHODS: Those with and without a family history were compared with respect to mammographic parenchymal pattern, interval cancer rates, mean sojourn time and sensitivity of screening. In the 358 cancers, the effect of family history was estimated on survival, incidence of advanced cancers and their relationship to screen detection. RESULTS: A significantly higher proportion of high risk mammographic patterns was observed in association with family history among women aged 40-49. Interval cancer rates were higher in women with a family history, and in older women at least, mean sojourn time was shortened in women with a family history (1.89 years compared to 2.70). Survival was better (although not significantly so) in cancers in women with a family history (relative hazard=0.52) independently of detection mode and was significantly poorer in interval cancers then screen detected cancers (relative hazard=2.72) independently of family history. Similarly, interval cancers tended to be larger, and worse malignancy grade in those with and without a family history of breast cancer. CONCLUSIONS: These results suggest that the policy often adopted of annual screening for woman aged 40-49, with a family history of breast cancer, is a reasonable one, and that it may also be necessary to shorten the inter-screening interval to one year in women aged over 50 but with a positive family history.
UI - 11221545
AU - Hou MF; Tsai KB; Fan HM; Wang CY; Lin WC; Liu CS; Lin HJ; Chai CY; Fu
TI - OY; Li SS; Chang YY; Huang TJ Familial breast cancer in southern Taiwan.
SO - Kaohsiung J Med Sci 2000 Aug;16(8):414-21
AD - Department of Surgery, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung, Taiwan.
The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non-familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease-free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed.
UI - 11248061
AU - Levy-Lahad E; Lahad A; Eisenberg S; Dagan E; Paperna T; Kasinetz L;
TI - Catane R; Kaufman B; Beller U; Renbaum P; Gershoni-Baruch R A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers.
SO - Proc Natl Acad Sci U S A 2001 Mar 13;98(6):3232-6
AD - Medical Genetics Unit, Shaare Zedek Medical Center and Hebrew University/Hadassah Medical School, P.O. Box 3235, Jerusalem 91031, Israel. email@example.com
BRCA1 and BRCA2 carriers are at increased risk for both breast and ovarian cancer, but estimates of lifetime risk vary widely, suggesting their penetrance is modified by other genetic and/or environmental factors. The BRCA1 and BRCA2 proteins function in DNA repair in conjunction with RAD51. A preliminary report suggested that a single nucleotide polymorphism in the 5' untranslated region of RAD51 (135C/G) increases breast cancer risk in BRCA1 and BRCA2 carriers. To investigate this effect we studied 257 female Ashkenazi Jewish carriers of one of the common BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) mutations. Of this group, 164 were affected with breast and/or ovarian cancer and 93 were unaffected. RAD51 genotyping was performed on all subjects. Among BRCA1 carriers, RAD51-135C frequency was similar in healthy and affected women [6.1% (3 of 49) and 9.9% (12 of 121), respectively], and RAD-135C did not influence age of cancer diagnosis [Hazard ratio (HR) = 1.18 for disease in RAD51-135C heterozygotes, not significant]. However, in BRCA2 carriers, RAD51-135C heterozygote frequency in affected women was 17.4% (8 of 46) compared with 4.9% (2 of 41) in unaffected women (P = 0.07). Survival analysis in BRCA2 carriers showed RAD51-135C increased risk of breast and/or ovarian cancer with an HR of 4.0 [95% confidence interval 1.6-9.8, P = 0.003]. This effect was largely due to increased breast cancer risk with an HR of 3.46 (95% confidence interval 1.3-9.2, P = 0.01) for breast cancer in BRCA2 carriers who were RAD51-135C heterozygotes. RAD51 status did not affect ovarian cancer risk. These results show RAD51-135C is a clinically significant modifier of BRCA2 penetrance, specifically in raising breast cancer risk at younger ages.
UI - 11385712
AU - Caluseriu O; Cordisco EL; Viel A; Majore S; Nascimbeni R; Pucciarelli S;
TI - Genuardi M Four novel MSH2 and MLH1 frameshift mutations and occurrence of a breast cancer phenocopy in hereditary nonpolyposis colorectal cancer.
SO - Hum Mutat 2001 Jun;17(6):521
AD - Istituto di Genetica Medica, Universita Cattolica del S. Cuore, Rome.
Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations of genes encoding for proteins of the mismatch repair (MMR) machinery. The majority of mutations occur in the MLH1 and MSH2 genes, and consist of splice-site, frameshift and nonsense changes, leading to loss of protein function. In this study, we screened 7 HNPCC families for MLH1/MSH2 mutations. Sequence changes were identified in 5 families. Four alterations were novel 1- or 2-bp deletions or insertions causing a frameshift and appearance of premature stop codons (MLH1: c.597-598delGA, c.1520-1521insT; MSH2: c.1444delA, c.119delG). The four small insertions/ deletions were located within stretches of simple repeated sequences. By reviewing the HNPCC mutation database, we found that the majority of 1-2 bp frameshift mutations similarly affects simple repetitive stretches, pointing to DNA polymerase slippage during replication as the most likely source of such errors. We also evaluated microsatellite instability (MSI) in a breast carcinoma (BC) from an MLH1 mutation carrier. While a colon cancer from the same individual showed MSI, the BC specimen was MSI-negative, indicating that development of the latter tumor was unrelated to MMR impairment, despite presence of a constitutional MLH1 mutation. Hum Mutat 17:521, 2001. Copyright 2001 Wiley-Liss, Inc.
UI - 11394499
AU - Di Modugno F; Buglioni S; Mottolese M; Bello DD; Cascioli S; Chersi A;
TI - Santoni A; Nistico P Polyclonal antibodies against gp185HER2 peptides: their putative role in the identification of a particular HER2 status in patients with breast cancer.
SO - J Immunother 2001 May-Jun;24(3):221-31
AD - Laboratory of Pathophysiology, CRS Regina Elena Cancer Institute, Rome, Italy.
The HER2 oncogene and its relative oncoprotein, gp185HER2, a transmembrane glycoprotein belonging to the epidermal growth factor receptor family, are overexpressed in a wide range of solid tumors including breast and ovarian cancer. In patients with breast cancer, both humoral and cell-mediated HER2 immune responses have been found as well as in some patients with gp185HER2 nonoverexpressing tumors. To establish whether peptide sequences identified as HLA-A2-restricted T-cell epitopes are expressed in breast tumor cell lines and tissues, we produced and characterized by different methodologic approaches polyclonal antibodies raised against four gp185HER2 peptides. Two of the antibodies recognized peptides eluted from the HLA-A2 groove of the mDAmB231 breast cancer cell line expressing a basal level of gp185HER2. Paraffin-embedded primary and metastatic breast tumors were specifically immunostained by all four reagents, thereby showing an overlapping reactivity. When this immunoreactivity was compared with that obtained using two different monoclonal antibodies, in 105 breast primary tumors and 36 corresponding lymph node metastases, we identified a subset of tumors that were negative with anti-gp185HER2 monoclonal antibodies and positive with the four antipeptide antibodies. Our novel observations provide in vivo evidence of the complexity involved in evaluating HER2 expression, and open a new path for understanding the biologic significance of HER2 status in breast tumors.
UI - 11432618
AU - Cardoso F; Di Leo A; Larsimont D; Gancberg D; Rouas G; Dolci S; Ferreira
TI - F; Paesmans M; Piccart M Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes.
SO - Ann Oncol 2001 May;12(5):615-20
AD - Jules Bordet Institute, Brussels, Belgium.
BACKGROUND: Breast cancer is a heterogeneous disease. Predictive biological markers (BM) of responsiveness to therapy need to be identified. Evaluation of BM is mainly done at the primary site. However, in the adjuvant therapy of breast cancer, the main goal is control of micrometastases. It is still unknown whether heterogeneity in the expression of BM between the primary site and its micrometastases exists. OBJECTIVE: To evaluate the expression of some BM with potential predictive value from the primary breast cancer site and metastatic ipsilateral axillary lymph nodes. PATIENTS AND METHODS: Focality (percentage of positive cells) and intensity staining scores were evaluated for each marker. Freshly cut sections (4 microm) from embedded blocks of breast cancer fixed in formalin or bouin were put onto superfrost slides (Menzel-Glaser). Protein expression was evaluated immunohistochemically (IHC) using monoclonal antibodies against: topo II-alpha (clone KiS1, 1 microg/ml, Roche) with a trypsine pre-treatment (P); HSP27 (clone G3.1, 1/60, Biogenex), HSP70 (clone BRM.22, 1/80, Biogenex) and HER2 (clone CB11, 1/40, Novocastra; without P); p53 (clone D07, 1/750, Dako) and bcl-2 (clone 124, 1/60, Dako) with citrate buffer as P. RESULTS: Overall, the percentage of discordant marker status in the primary tumour and its metastatic lymph nodes was 2% for HER2, 6% for p53, 15% for bcl-2, 19% for topoisomerase II-alpha, 24% for HSP27 and 30% for HSP70. For the subgroup of patients with positive BM in the primary tumour, the percentage of discordance was 6% for HER2, 7% for p53, 14% for bcl-2, 19% for HSP70, 21% for topoisomerase II-alpha and 36% for HSP27. For the subgroup of patients with positive BM in the lymph nodes, the percentage of discordance was 9% for bcl-2, 15% for HER2 and p53, 21% for topoisomerase II-alpha, 22% for HSP27 and 25% for HSP70. CONCLUSIONS: 1) No biological marker had 100% concordant results. 2) Although some discordant cases might be explained by the limitations of the IHC technique, future studies aiming to evaluate the predictive value of BM in the adjuvant therapy of breast cancer should take into account a possible difference in BM expression between the primary and the metastatic sites.
UI - 11434504
AU - Yim DS; Parkb SK; Yoo KY; Yoon KS; Chung HH; Kang HL; Ahn SH; Noh DY;
TI - Choe KJ; Jang IJ; Shin SG; Strickland PT; Hirvonen A; Kang D Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer.
SO - Pharmacogenetics 2001 Jun;11(4):279-86
AD - Department of Pharmacology, Gachon Medical School, Inchon, Korea.
A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. One hundred and sixty-three histologically confirmed incident breast cancer cases and 163 age- and menopausal status-matched control individuals with no present or previous history of cancer were selected as study subjects. COMT genetic polymorphism was determined by gel electrophoresis after NlaIII enzyme digestion of amplified DNA. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Women with at least one COMT lower enzyme activity associated allele (COMT-L) were at elevated risk for breast cancer (OR = 1.7, 95% CI = 1.04-2.78) compared with those homozygous for high enzyme activity associated COMT-H alleles. Among women with low (> or = 23.1) body mass index the COMT-L allele containing genotypes posed a marginally significant increased risk of breast cancer compared to the COMT-HH genotype (OR = 1.8, 95% CI = 0.95-3.48). Women with at least one COMT-L allele who had experienced a full-term pregnancy when aged over 30 years or were nulliparous had 2.7-fold increased risk; however, this increase did not reach statistical significance (OR = 2.7, 95% CI = 0.64-11.35). Furthermore, never-drinking and never-smoking women with at least one COMT-L allele were at increased risk of breast cancer compared to those with COMT-HH genotype with ORs of 2.0 (95% CI = 1.23-3.38) and 1.7 (95% CI = 1.04-2.62), respectively. These results are consistent with studies showing that COMT genotype of lower enzyme activity might be related to increase in risk of breast cancer, and extend this finding to Korean women.
UI - 11434389
AU - Campos B; Diez O; Cortes J; Domenech M; Pericay C; Alonso C; Baiget M
TI - Conditions for single-strand conformation polymorphism (SSCP) analysis of BRCA1 gene using an automated electrophoresis unit.
SO - Clin Chem Lab Med 2001 May;39(5):401-4
AD - Servei de Genetica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
The single-strand conformation polymorphism procedure has been applied in routine testing for hereditary diseases and cancer. However, temperature, running time, gel composition, fragment length, etc. can influence its sensitivity. Mutation detection in the clinical setting depends on the development of automated technology, especially for large genes such as the breast cancer gene BRCA1. We analysed DNA samples with BRCA1 mutations in an automated system (GenePhor System; Amersham-Pharmacia Biotech, Uppsala, Sweden). The concentrations of DNA template and PCR primers, the effect of chilling after denaturation, and the temperature and time of the electrophoresis were investigated. All band-shifts were detected by electrophoresis at 5 degrees C for 2 h 15 min. Concentrations of DNA and samples used in the PCR did not affect the SSCP pattern, but chilling the PCR product in ice after denaturation was required. The type and position of mutation in the fragments did not influence the probability of a mobility shift, although SSCP analysis was more sensitive for fragments shorter than 350 bp. This automated SSCP method meets the requirements of fast turnaround and sensitivity and can be readily adapted to the screening of large genes such as BRCA1.
UI - 11437066
AU - Carter RF
TI - BRCA1, BRCA2 and breast cancer: a concise clinical review.
SO - Clin Invest Med 2001 Jun;24(3):147-57
AD - Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ont.
Less than 5% of breast cancers are hereditary, but over 90% of hereditary breast cancers are caused by a mutation of either BRCA1 or BRCA2. The mutation may be inherited from either the maternal or the paternal side of the family. Clinicians should consider specific criteria in the family history to determine when a patient may benefit from counselling and appropriate testing. Testing is generally offered only to patients who are at high risk and is currently estimated to have a sensitivity of about 85%. Test protocols are primarily oriented to detecting frameshift and nonsense mutations that cause premature protein truncations. Missense mutations also occur, but they are less common and sometimes not clearly of clinical significance. Laboratory results need to be correlated with the clinical picture, and genetic counselling is a critical component in maximizing the benefits of testing. In the future, application of more refined clinical criteria, as well as expected improvements in laboratory techniques, will undoubtedly lead to significantly better outcomes and options in surveillance and management for hereditary breast and ovarian cancer syndromes caused by mutations of BRCA1 and BRCA2.
UI - 11474658
AU - Mahavni V; Kim SC; Benda TA; Sanders L; Buller RE
TI - The androgen receptor and DXS15-134 markers show a high rate of discordance for germline X chromosome inactivation.
SO - J Med Genet 2001 Jul;38(7):474-8
UI - 11453492
AU - Setoguchi A; Okuda M; Nishida E; Yazawa M; Ishizaka T; Hong SH; Hisasue
TI - M; Nishimura R; Sasaki N; Yoshikawa Y; Masuda K; Ohno K; Tsujimoto H Results of hyperamplification of centrosomes in naturally developing tumors of dogs.
SO - Am J Vet Res 2001 Jul;62(7):1134-41
AD - Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, University of Tokyo, Japan.
OBJECTIVE: To evaluate results of centrosome hyperamplification in naturally developing tumors of dogs. SAMPLE POPULATION: Tumor specimens from 9 dogs with tumors (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, and mammary gland tumor) and 2 canine osteosarcoma cell lines. PROCEDURE: 3 antibodies for centrosome proteins (ie, anti-gamma-tubulin, anti-BRCA1, and anti-pericentrin) were used for immunohistochemical analysis. Double immunostaining for centrosomes was used to confirm the specificity of these antibodies for centrosomes. Mutational analysis of the canine p53 gene was carried out by polymerase chain reaction-single-strand conformation polymorphism analysis, and expression of canine MDM2 protein was evaluated by use of immunohistochemical analysis, using anti-MDM2 antibody. RESULTS: Immunohistochemical analysis of dog osteosarcoma cell lines with apparent aneuploidy revealed frequent hyperamplification of centrosomes in the osteosarcoma cell lines. Similar hyperamplified centrosomes were detected in the tumor tissues from all of the 9 tumors. The frequency of cells with hyperamplified centrosomes (3 to 20/cell) in each tumor tissue ranged from 9.50 to 48.1%, whereas centrosome hyperamplification was not observed in normal lymph nodes from these dogs. In 8 of the 9 tumors, mutation of p53 gene or overexpression of MDM2, or both, was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Various types of naturally developing tumors in dogs often have hyperamplification of centrosomes associated with chromosome instability. Hyperamplification of centrosomes is a novel tumor marker for use in cytologic and histologic examinations of clinical specimens obtained from dogs.
UI - 11445874
AU - Naidu R; Wahab NA; Yadav M; Kutty MK; Nair S
TI - Detection of amplified int-2/FGF-3 gene in primary breast carcinomas using differential polymerase chain reaction.
SO - Int J Mol Med 2001 Aug;8(2):193-8
AD - International Medical University, Sesama Centre, Plaza Komenwel, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. firstname.lastname@example.org
Amplification of int-2/FGF-3 gene was investigated by differential polymerase chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these, 23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33 were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non-comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions. A significant association was observed between int-2 amplification in the in situ components and adjacent invasive lesion (P<0.05). All tumors with int-2 amplification in the in situ lesions (7/7) also demonstrated same degree of amplification in the adjacent invasive components. However, 9% (5/53) of the tumors with no amplified int-2 gene in the in situ components showed int-2 amplification in the adjacent invasive lesions. A significant relationship was noted between amplification of int-2 and lymph node metastases (P<0.05) and poorly differentiated tumors (P<0.05) but not with estrogen receptor status (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority of the patients belong to younger age group (<50 years old) but a comparison of the age groups showed that the amplification of int-2 was not statistically associated with patient age (P>0.05). These observations indicate that amplification of int-2 tends to strengthen the view that int-2 may have the potential to be an indicator of poor prognosis regardless of the age of the patient. Moreover, the presence of int-2 amplification in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that int-2 could be a marker of genetic instability occurring in early and late stages of tumor development.
UI - 11456268
AU - Shibata A; Hayashi Y; Imai T; Funahashi H; Nakao A; Seo H
TI - Somatic gene alteration of AIB1 gene in patients with breast cancer.
SO - Endocr J 2001 Apr;48(2):199-204
AD - Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Japan.
AIB1 (amplified in breast cancer 1) is a coactivator which stimulates the transcriptional activity of the liganded-estrogen receptor (ER). It has been reported that AIBI gene is amplified and overexpressed in some breast cancer cell lines. AIB1 contains a stretch of homopolymeric glutamines (poly-Q). We reported that the poly-Q shows polymorphism, which provides an opportunity to study somatic gene alteration such as loss of heterozygosity (LOH). In the present study, we aimed to investigate the frequency of somatic gene alteration in Japanese patients with breast cancer. Amplification of AIB1 gene was detected only in 1 (2.6%) of 39 breast cancer tissues by DNA dot blot analysis. On the other hand, LOH was found in 2 (8%) breast cancer tissues out of 25 patients showing heterozygosity in peripheral blood mononuclear cells (PBMC). Taken together, both LOH and amplification of AIB1 gene were identified in breast cancer patients, raising the possibility that AIB1 have oncogenic as well as antioncogenic potential for the pathogenesis of breast cancer.
UI - 11467450
AU - Callahan R; Raafat A
TI - Notch signaling in mammary gland tumorigenesis.
SO - J Mammary Gland Biol Neoplasia 2001 Jan;6(1):23-36
AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. email@example.com
The Notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. Recent studies suggest that, depending on the cellular and developmental context, Notch signaling may also affect cell proliferation and programmed cell death. Mammals have four related Notch genes. One of these, designated Notch-4, was found to