National Cancer Institute, Aviano, PN, Italy.
Cancer Metastasis Rev. 2012 Jun;31(1-2):131-42. doi: 10.1007/s10555-011-9336-6.
Mutations in the BRCA1 tumor suppressor predispose to the development of breast and ovarian cancers. Noticeably, the majority of BRCA1-associated breast cancers are triple-negative (ER-, PR- and HER2-) and display a basal-like phenotype, which are features relatively uncommon among sporadic breast cancers. It is well documented that BRCA1 is involved in a number of cellular functions converging to the maintenance of genomic stability. However, the control over DNA integrity does not seem to account for the peculiar phenotype of BRCA1-associated tumors since mutations in other genes involved in such a function, namely BRCA2, associate to a broader spectrum of breast carcinoma subtypes. Indeed, an increasing body of evidence indicates that BRCA1 is implicated also in the regulation of transcription by impinging upon general components of the transcriptional machinery. Thus, elucidating the complex biochemical network regulated by BRCA1 may allow a better understanding also of the biology of sporadic triple-negative/basal-like tumors and lay down the basis for novel preventive measures and more effective therapeutic strategies. This review summarizes recent findings on the role of BRCA1 in the regulation of transcription and how this might set the ground for the development of cancers with triple-negative/basal-like features.
BRCA1 肿瘤抑制基因突变易导致乳腺癌和卵巢癌的发生。值得注意的是,大多数与 BRCA1 相关的乳腺癌为三阴性(ER-、PR- 和 HER2-),表现出基底样表型,这在散发性乳腺癌中相对少见。已有大量文献证明 BRCA1 参与了许多细胞功能,这些功能汇聚到维持基因组稳定性。然而,对 DNA 完整性的控制似乎并不能解释与 BRCA1 相关的肿瘤的特殊表型,因为参与这种功能的其他基因(如 BRCA2)的突变与更广泛的乳腺癌亚型相关。事实上,越来越多的证据表明,BRCA1 还通过影响转录的一般组件来参与转录的调节。因此,阐明 BRCA1 调节的复杂生化网络可能有助于更好地理解散发性三阴性/基底样肿瘤的生物学特性,并为新的预防措施和更有效的治疗策略奠定基础。这篇综述总结了 BRCA1 在转录调控中的作用的最新发现,以及这可能为具有三阴性/基底样特征的癌症的发展奠定基础。