Department of Pathology & Laboratory Medicine, The University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Front Biosci (Landmark Ed). 2013 Jun 1;18(4):1445-59. doi: 10.2741/4191.
The familial aggregation of prostate cancer and breast cancer has been observed for almost half a century and about 85% of the inherited breast cancer can be linked to germ-line mutations of BRCA1 (breast cancer 1, early onset) and BRCA2. In this review, we are mainly focusing on the contribution of BRCA1/2 sequence variations to prostate cancer risk and disease progression. We will discuss the biological functions of BRCA1/2 and BRCA1/2-related signaling pathways in prostate cancer biology. The majority of studies supporting the link between BRCA1/2 mutations and prostate cancer are from populations with a high frequency of mutations, such as Ashkenazi Jewish, Icelandic, and U.K. population. BRCA1 can directly interact with the androgen receptor (AR) and Janus kinase (JAK), and can differentially regulate insulin-like growth factor 1 receptor (IGF-IR) expression in an AR-dependent manner. BRCA2 homeostasis in prostate cancer cells has been found to be critical in determining cell fates during prostate cancer progression. This review may be helpful for medical professionals and prostate cancer patients when discussing prostate cancer risks, treatment and prognosis.
前列腺癌和乳腺癌的家族聚集现象已经观察了近半个世纪，大约 85%的遗传性乳腺癌可以与 BRCA1（乳腺癌 1 型，早发）和 BRCA2 的种系突变相关。在这篇综述中，我们主要关注 BRCA1/2 序列变异对前列腺癌风险和疾病进展的影响。我们将讨论 BRCA1/2 在前列腺癌生物学中的生物学功能和 BRCA1/2 相关信号通路。大多数支持 BRCA1/2 突变与前列腺癌之间关联的研究来自突变频率较高的人群，如阿什肯纳兹犹太人群、冰岛人群和英国人群。BRCA1 可以直接与雄激素受体（AR）和 Janus 激酶（JAK）相互作用，并以 AR 依赖的方式差异调节胰岛素样生长因子 1 受体（IGF-IR）的表达。BRCA2 在前列腺癌细胞中的动态平衡对于确定前列腺癌进展过程中的细胞命运至关重要。当讨论前列腺癌风险、治疗和预后时，这篇综述可能对医疗专业人员和前列腺癌患者有所帮助。
