The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues

Marquis, Sandra T.; Rajan, Jayant V.; Wynshaw‐Boris, Anthony; Xu, Junzhe; Yin, Gui Ying; Abel, Kenneth; Weber, Barbara; Chodosh, Lewis A.

doi:10.1038/ng0995-17

Cited by 317 publications

(270 citation statements)

References 22 publications

Supporting

Mentioning

242

Contrasting

Order By: Relevance

“…The human BRCA1 gene encodes an 1863 amino acid nuclear protein that is expressed in a wide variety of adult human tissues (Marquis et al, 1995). Evidence implicates a role for BRCA1 in the control gene expression.…”

Section: Introductionmentioning

confidence: 99%

BRCA1 physically associates with p53 and stimulates its transcriptional activity

et al. 1998

View full text Add to dashboard Cite

Mutations of the BRCA1 tumor suppressor gene are the most commonly detected alterations in familial breast and ovarian cancer. Although BRCA1 is required for normal mouse development, the molecular basis for its tumor suppressive function remains poorly understood. We show here that BRCA1 increases p53-dependent transcription from the p21 WAF1/CIP1 and bax promoters. We also show that BRCA1 and p53 proteins interact both in vitro and in vivo. The interacting regions map, in vitro, to aa 224 ± 500 of BRCA1 and the C-terminal domain of p53. Tumor-derived transactivation-de®cient BRCA1 mutants are defective in co-activation of p53-dependent transcription and a truncation mutant of BRCA1 that retains the p53-interacting region acts as a dominant inhibitor of p53-dependent transcription. BRCA1 and p53 cooperatively induce apoptosis of cancer cells. The results indicate that BRCA1 and p53 may coordinately regulate gene expression in their role as tumor suppressors.

show abstract

Section: Introductionmentioning

confidence: 99%

BRCA1 physically associates with p53 and stimulates its transcriptional activity

et al. 1998

View full text Add to dashboard Cite

show abstract

“…The expression pattern of BRCA1 in the mouse has suggested that this gene plays a role in proliferation and di erentiation of a wide variety of tissues, and particularly that of the breast (Lane et al, 1995;Marquis et al, 1995). BRCA1 expression is also increased in proliferating cells (Gudas et al, 1996;Marks et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

GA-binding protein α/β is a critical regulator of the BRCA1 promoter

et al. 2000

View full text Add to dashboard Cite

Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced e ect in T47D cells. The main transcription factor interacting with this site was identi®ed as GABPa/b, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPa and b1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPa/b is a critical activator of BRCA1 expression, and that its activity may di er in human breast cell lines.

show abstract

“…These two hypotheses, which are not mutually exclusive, stress that BRCA1 may have an important role in cellular di erentiation and proliferation. Direct evidence for an essential role of BRCA1 in mammalian development has been obtained from transgenic mice, since homozygous disruption of the BRCA1 gene results in embryonic lethality (Hakem et al, 1996), and the progressive changes of BRCA1 expression during mouse embryogenesis also imply a role for BRCA1 in the di erentiation process (Marquis et al, 1995). Alteration of the BRCA1 mRNA level has been observed in sporadic breast cancers, microdissections of biopsies from sporadic invasive breast tumors have shown a decrease in BRCA1 expression in the tumoral component of the samples (Thompson et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of BRCA1 in human sporadic breast cancer; analysis of DNA methylation patterns of the putative promoter region

et al. 1998

View full text Add to dashboard Cite

Germ-line alterations of BRCA1 are responsible for about 50% of familial breast cancers. Although its biological function (s) has not yet been fully determined, it has been suggested that it may act as a tumor suppressor gene in breast and ovarian cancers. In sporadic breast cancers alterations of BRCA1 have not been detected and in vitro experiments have indicated that BRCA1 negatively regulates cellular proliferation. The present study was designed to identify and quantify, the BRCA1 mRNA levels, in normal and neoplasic human breast tissue. BRCA1 mRNA molecules were quanti®ed using competitive reverse transcriptase PCR assays. DNA methylation patterns of this gene have been analysed by Southern blot experiments using methylation sensitive restriction enzymes. We found that BRCA1 mRNA levels were signi®cantly lower in sporadic breast cancers (37 cases analysed, 24 cases of invasive ductal carcinomas not otherwise speci®ed (NOS), two lobular carcinomas in situ two medullary carcinomas, four invasive lobular carcinomas, two invasive mucinous carcinomas and three invasive ductal carcinomas with predominantly in situ component) compared with normal breast tissues (P=0.0003). This down-regulation of BRCA1 is observed in all histologic types analysed. In invasive ductal carcinomas NOS, this down-regulation does not correlate with any of the prognostic factors studied (tumor size, node status, histologic grade, hormone receptor status). In the samples analysed, alterations of DNA methylation patterns were not dectected in the vicinity of the major transcription start site. These data suggest the involvement of BRCA1 in the carcinogenesis of these histologic types.

show abstract

The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues

Cited by 317 publications

References 22 publications

BRCA1 physically associates with p53 and stimulates its transcriptional activity

BRCA1 physically associates with p53 and stimulates its transcriptional activity

GA-binding protein α/β is a critical regulator of the BRCA1 promoter

Down-regulation of BRCA1 in human sporadic breast cancer; analysis of DNA methylation patterns of the putative promoter region

Contact Info

Product

Resources

About