BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions

Yarden, Ronit I.; Papa, Moshe Z.

doi:10.1158/1535-7163.mct-05-0471

Cited by 59 publications

(46 citation statements)

References 73 publications

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“…37 BRCA1 has many cellular functions in addition to DNA repair, 38 including transcriptional regulation of hTERT 39 and TP53 40 and RB1-mediated cell cycle control. 41 …”

Section: Cell Adhesionmentioning

confidence: 99%

Human papillomavirus and molecular considerations for cancer risk

Whiteside

Siegel

Unger

2008

Cancer

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Human papillomaviruses (HPVs) are a major cause of cancer globally, including cervical cancer. The HPV 'early' proteins, E6 and E7, are the chief oncoproteins involved in cancer progression. These oncoproteins are more highly expressed in high-grade dysplasias and invasive cancer coincident with reduced viral DNA replication and reduced production of infective progeny virions. The E6 and E7 oncoproteins interact with several cellular proteins-classically TP53 and RB1, respectively-leading to the degradation of several of these proteins, although all interactions do not necessarily result in the degradation of a cellular protein.HPV infection is also associated with viral and host DNA methylation changes, many of which also occur in cancer types not associated with HPV infection. The E6 and E7 interactions with cellular proteins and DNA methylation changes are associated with changes in the integrity of key cellular pathways that regulate genomic integrity, cell adhesion, the immune response, apoptosis, and cell cycle control. The alterations in key cellular pathways may provide useful biomarkers to improve the sensitivity of current cancer screening methods, such as the Papanicolaou test. This review provides a detailed summary of the interactions of E6 and E7 with cellular proteins and alterations in cellular DNA methylation associated with HPV infection. The importance of molecular biomarkers to the clinical setting, underserved populations, and general public health is discussed.

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“…37 BRCA1 has many cellular functions in addition to DNA repair, 38 including transcriptional regulation of hTERT 39 and TP53 40 and RB1-mediated cell cycle control. 41 …”

Section: Cell Adhesionmentioning

confidence: 99%

Human papillomavirus and molecular considerations for cancer risk

Whiteside

Siegel

Unger

2008

Cancer

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“…It has been implicated in normal cellular functions including cell cycle regulation, replication, mitotic spindle assembly, transcription regulation and higher chromatin hierarchical control 5 . Also BRCA1 plays a central role in DNA damage response (DDR) through direct interaction with DDR proteins, as well as by regulation of gene transcription 6 .…”

Section: Introductionmentioning

confidence: 99%

“…Germline mutations of BRCA1 have been associated with increased risk of breast, ovarian, and more recently, prostate cancer [6][7][8] . Breast cancers arising in patients with BRCA1 mutations are usually high grade, poorly differentiated tumors, characteristically rapid progression without an in situ component, higher incidence of metastasis and poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

Gachechiladze¹,

Überall²,

Kolek³

et al. 2013

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress. Methods. We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases. Results. BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases. Conclusion.The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.

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“…BRCA1 is an important regulatory protein. It is involved in the regulation of the cell cycle, DNA damage repair, transcription and chromatin remodeling (Starita and Parvin, 2003;Deng, 2006;Ko et al, 2006;Mullan et al, 2006;Rosen et al, 2006;Yarden and Papa, 2006). Recent evidence revealed a role of BRCA1 in the regulation of numeral homeostasis of centrosomes (Indraccolo et al, 2006;Ouchi, 2006).…”

Section: Introductionmentioning

confidence: 99%

MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene

et al. 2007

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Metastasis-associated tumor antigen 1 (MTA1), a component of the nucleosome remodeling and deacetylating (NuRD) complex is routinely upregulated in several cancers. In the present study, we investigated the potential role of MTA1 in BRCA1 transcriptional repression and subsequent chromosomal instability. MTA1-NuRD complex was found to negatively regulate BRCA1 transcription by physically associating with an atypical estrogen-responsive element (ERE) on the BRCA1 promoter. Moreover, MTA1 and HDAC complex recruited to the ERE of BRCA1 promoter in an ER a-dependent manner. Accordingly, BRCA1 protein levels were enhanced by silencing of either MTA1 expression or by treatment with the specific histone deacetylase inhibitor trichostatin A. MTA1's strong repressive effects on BRCA1 expression was supported by our observation that cells stably overexpressing MTA1 showed centrosome amplification which has been long implicated as a phenotype for BRCA1 repression. Accordingly, overexpression of BRCA1 in cells stably over expressing MTA1 resulted in restoration of normal centrosome numbers. Together, these findings strongly implicate MTA1 in the transcriptional repression of BRCA1 leading to abnormal centrosome number and chromosomal instability.

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BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions

Cited by 59 publications

References 73 publications

Human papillomavirus and molecular considerations for cancer risk

Human papillomavirus and molecular considerations for cancer risk

Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene

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