BRCA1 Pathway Function in Basal-Like Breast Cancer Cells

Hill, Sarah J.; Clark, Allison; Silver, Daniel P.; Livingston, David M.

doi:10.1128/mcb.01646-13

Cited by 42 publications

(50 citation statements)

References 69 publications

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“…BRCA1 mutant alleles are often capable of generating truncated BRCA1 proteins that lack functional domains usually present in the full-length protein (Drost etal., 2016; Hill et al, 2014; Johnson et al, 2013; Wang et al, 2016a, 2016b; Zhou et al, 2003). To examine the DSB recruitment dynamics of BRCA1 proteins that are deficient for various functional domains, we examined γ-irradiation-induced foci (IRIF) formation kinetics.…”

Section: Resultsmentioning

confidence: 99%

BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance

et al. 2018

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SUMMARY BRCA1 functions in homologous recombination (HR) both up- and downstream of DNA end resection. However, in cells with 53BP1 gene knockout (KO), BRCA1 is dispensable for the initiation of resection, but whether BRCA1 activity is entirely redundant after end resection is unclear. Here, we found that 53bp1 KO rescued the embryonic viability of a Brea1ΔC/ΔC mouse model that harbors a stop codon in the coiled-coil domain. However, Brca1ΔC/ΔC;53bp1−/− mice were susceptible to tumor formation, lacked Rad51 foci, and were sensitive to PARP inhibitor (PARPi) treatment, indicative of suboptimal HR. Furthermore, BRCA1 mutant cancer cell lines were dependent on truncated BRCA1 proteins that retained the ability to interact with PALB2 for 53BP1 KO induced RAD51 foci and PARPi resistance. Our data suggest that the overall efficiency of 53BP1 loss of function induced HR may be BRCA1 mutation dependent. In the setting of 53BP1 KO, hypomorphic BRCA1 proteins are active downstream of end resection, promoting RAD51 loading and PARPi resistance.

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Section: Resultsmentioning

confidence: 99%

BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance

et al. 2018

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“…Lesions in other DNA repair pathways including base excision repair and inter-strand crosslink (ICL) repair also have the significantly roles in TNBC. 25,26 The comprehensive illustration of main pathways involved in platinum-induced DNA damage repair in breast cancer is shown in Fig. 1B.…”

Section: Molecular Mechanisms Of Platinum and Homologous Recombinatiomentioning

confidence: 99%

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Jin

Zhang

et al. 2017

Cancer Biology & Therapy

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Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC. BRCA mutation and methylation have been demonstrated to be important potential biomarkers. Based on genome-wide effects, BRCA-like classifier can identify the functional loss of BRCA and work as the predictor. HRD score that is able to identify the "BRCAness" and predict the sensitivity of platinum is increasingly considered. Taken together, all findings suggest that HR deficiency profile encompassed by BRCA mutation and high HRD score could predict response to platinum, even to other DNA-damage inducing agents. p53 family members and molecular subtypes of TNBC are also important alternative considerations for predicting platinum response based on the preclinical trials. Currently, tumor infiltrating lymphocyte level and thrombocytopenia are emerging as predictive biomarkers.

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“…Breast cancer type 1 susceptibility protein (BRCA1), a well‐known tumor suppressor with multiple interacting partners, is predicted to have diverse biological functions 8, 9, 10. However, the role of BRCA1 in protecting cardiac tissue from DNA damage has not been fully explored to date.…”

mentioning

confidence: 99%

Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein

Fan

Liu

Fang

et al. 2016

JAHA

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BackgroundThe polyphenol resveratrol (Rev) has been reported to exhibit cardioprotective effects, such as inhibition of TAC (transverse aortic constriction) or isoprenaline (ISO)‐induced hypertrophy. MicroRNA‐155 (miR‐155) was found to be decreased in hypertrophic myocardium, which could be further reduced by pretreatment of Rev. The study was designed to investigate the molecular effects of miR‐155 on cardiac hypertrophy, focusing on the role of breast cancer type 1 susceptibility protein (BRCA1).Methods and ResultsWe demonstrated that Rev alleviated severity of hypertrophic myocardium in a mice model of cardiac hypertrophy by TAC treatment. Down‐regulation of miR‐155 was observed in pressure overload– or ISO‐induced hypertrophic cardiomyoctyes. Interestingly, administration of Rev substantially attenuated miR‐155 level in cardiomyocytes. In agreement with its miR‐155 reducing effect, Rev relieved cardiac hypertrophy and restored cardiac function by activation of BRCA1 in cardiomyoctyes. Our results further revealed that forkhead box O3a (FoxO3a) was a miR‐155 target in the heart. And miR‐155 directly repressed FoxO3a, whose expression was mitigated in miR‐155 agomir and mimic treatment in vivo and in vitro.ConclusionsWe conclude that BRCA1 inactivation can increase expression of miR‐155, contributing to cardiac hypertrophy. And Rev produces their beneficial effects partially by down‐regulating miR‐155 expression, which might be a novel strategy for treatment of cardiac hypertrophy.

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BRCA1 Pathway Function in Basal-Like Breast Cancer Cells

Cited by 42 publications

References 69 publications

BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance

BRCA1 Mutation-Specific Responses to 53BP1 Loss-Induced Homologous Recombination and PARP Inhibitor Resistance

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

Resveratrol Ameliorates Cardiac Hypertrophy by Down‐regulation of miR‐155 Through Activation of Breast Cancer Type 1 Susceptibility Protein

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