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• W2068239457 abstract "Predisposition to breast cancer has been attributed to mutantBRCA1alleles whereas noBRCA1mutation has been described yet in sporadic breast tumours. As an initial characterization of the regulation and function of theBRCA1gene in sporadic breast cancer, we have compared the expression ofBRCA1in thirty-five paired tumour specimens versus their corresponding adjacent normal tissue. We found two- to five-fold reducedBRCA1expression levels in tumour specimens as compared to normal tissue. DecreasedBRCA1expression was significantly associated with loss of heterozygosity (LOH) at theBRCA1region, as well as with negative estrogen receptor (ER) status. Our results offer an alternative explanation of howBRCA1could play an important role in sporadic breast cancer, not via mutations in coding sequences but due to transcriptional disregulation. DecreasedBRCA1mRNA may be caused due to loss of gene copies, deletions of regulatory elements in theBRCA1promoter or failure of transcriptional regulation by estrogen receptors. We also investigated possible relationships betweenBRCA1, p53, mdm-2andp21WAF1/CIP1at the expression level.p53expression was unaffected in almost all the specimens,mdm-2was overexpressed in 18/35 specimens while 21/35 overexpressedp21.Samples exhibiting reducedBRCA1levels simultaneously overexpressed bothp21andmdm-2,showing thatBRCA1,at certain levels, even reduced up to 2.7-fold, is functional and sufficient to upregulatep21,when p53 activity is inhibited by its negative regulator, themdm-2.On the contrary, specimens exhibiting more than 2.7-fold reducedBRCA1levels, overexpressedp21whilemdm-2expression was normal, allowing us to speculate thatp21transcriptional activation is due to p53 activity, in cases with dramatically decreasedBRCA1expression. Our findings provide evidence, indicating that BRCA1 might affect cell cycle regulation and loss of BRCA1 function due to decreased expression leads to cell cycle arrest, throughp53andp21genes." @default.
• W2068239457 created "2016-06-24" @default.
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• W2068239457 date "1998-04-01" @default.
• W2068239457 modified "2023-10-14" @default.
• W2068239457 title "DecreasedBRCA1Expression Levels May Arrest the Cell Cycle through Activation ofp53Checkpoint in Human Sporadic Breast Tumors" @default.
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• W2068239457 doi "https://doi.org/10.1006/bbrc.1998.8379" @default.
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