Quantification of BRCA1 protein in sporadic breast carcinoma with or without loss of heterozygosity of theBRCA1 gene

Rio, Pascale; Maurizis, Jean‐Claude; Latour, Monique Peffault De; Bignon, Yves‐Jean; Bernard‐Gallon, Dominique

doi:10.1002/(sici)1097-0215(19990315)80:6<823::aid-ijc5>3.0.co;2-3

Cited by 47 publications

(2 citation statements)

References 16 publications

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“…In contrast, BRCA1 mutations are rare in sporadic cancers [2]. Nevertheless, sporadic breast cancers represent up to 90% of breast cancers and are often characterized by decreased BRCA1 expression at mRNA and protein levels [3] [4] [5].…”

Section: Introductionmentioning

confidence: 99%

BRCA1-Dependent Translational Regulation in Breast Cancer Cells

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et al. 2013

PLoS ONE

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BRCA1 (Breast Cancer 1) has been implicated in a number of cellular processes, including transcription regulation, DNA damage repair and protein ubiquitination. We previously demonstrated that BRCA1 interacts with PABP1 (Poly(A)-Binding Protein 1) and that BRCA1 modulates protein synthesis through this interaction. To identify the mRNAs that are translationally regulated by BRCA1, we used a microarray analysis of polysome-bound mRNAs in BRCA1-depleted and non-depleted MCF7 cells. Our findings show that BRCA1 modifies the translational efficiency of approximately 7% of the mRNAs expressed in these cells. Further analysis revealed that several processes contributing to cell surveillance such as cell cycle arrest, cell death, cellular growth and proliferation, DNA repair and gene expression, are largely enriched for the mRNAs whose translation is impacted by BRCA1. The BRCA1-dependent translation of these species of mRNAs therefore uncovers a novel mechanism through which BRCA1 exerts its onco-suppressive role. In addition, the BRCA1-dependent translation of mRNAs participating in unexpected functions such as cellular movement, nucleic acid metabolism or protein trafficking is indicative of novel functions for BRCA1. Finally, this study contributes to the identification of several markers associated with BRCA1 deficiency and to the discovery of new potential anti-neoplastic therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

BRCA1-Dependent Translational Regulation in Breast Cancer Cells

Dacheux

Vincent

Nazaret³

et al. 2013

PLoS ONE

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“…are known to contribute to the development of hereditary breast and ovarian cancers, BRCA1 mutations in sporadic breast cancers, which account for approximately 90% of all breast cancers, are surprisingly rare . In this aspect, various studies have indicated that loss of BRCA1 expression through epigenetic mechanisms may contribute about 10% of sporadic breast cancer Rio et al, 1999;Yang et al, 2001). In addition, accumulating evidence suggests that dysfunction of other genes, coding for proteins in pathways complementary to BRCA1, may be important in the pathogenesis of a significant proportion of sporadic, non-hereditary cancers.…”

Section: Role Of Brca1 and Associated Proteins In Breast Cancer Etiologymentioning

confidence: 99%

Antibody-Mediated BRCC36 Silencing: A Novel Approach for Targeted Breast Cancer Therapy

Chen¹

2009

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to Breast tumor cells with defective BRCA1 are believed to be more sensitive to the DNA-damage based therapies. We propose that the aberrant expression (gain or loss) or activity of protein(s) in BRCA1-associated pathways will lead to a BRCA1 null-like phenotype and DNA damage hypersensitivity in breast cancer cells. BRCC36, one of the novel BRCC subunits, has been found to be associated with BRCA1 and to play an important role in the regulation of BRCC ubiquitin E3 ligase activity. We have shown that BRCC36 expression is elevated in the majority of invasive breast tumors. Importantly, we have also demonstrated that depletion of BRCC36 resulted in hypersensitivity in breast cancer cells to IR and disruption of IR-induced BRCA1 activation. Based upon these findings, we believe that BRCC36 may be an ideal target for breast cancer therapy using the siRNA gene silencing approach. In proposed studies, we will apply a cancer cell-specific or "smart" therapeutic approach utilizing C6.5db-P/siRNA conjugates. Overall, the proposed studies will not only establish BRCC36 as a novel therapeutic target to enhance the efficacy of radiation and chemotherapy, but also help develop a novel strategy for targeting therapy aimed at improving the treatment of this prevalent and deadly disease. Body 6 Key Research Accomplishments 10 Reportable Outcomes 10 Conclusion 11 References 11 Appendices 13 BRCC36 Using a combination of affinity purification of anti-FLAG and mass spectrometric sequencing, we have reported a novel multiprotein complex, termed BRCC (BRCA1/2 Containing Complex), which contains seven polypeptides including BRCA1, BRCA2, BARD1 and RAD51 (Dong, et al., 2003). We first reported that BRCC was an E3 ubiquitin ligase complex exhibiting activities in the E2dependent ubiquitination of the tumor suppressor p53. In this multiprotein complex, three proteins, referred to as BRCC36, BRCC45, and BRCC120 have been found to be associated with BRCA1 and BRCA2. Among these novel BRCC genes, BRCC36/c6.1A gene is located at the Xq28 locus, a chromosomal break point in patients with prolymphocytic T-cell leukemia (T-PLL) (Fisch, et al., 1993). The chromosomal break occurred in two different introns of BCC36/c6.1A and the fusion transcripts were expressed at high levels in the leukaemic cells f...

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