Connection between Tumor Suppressor BRCA1 and PTEN in Damaged DNA Repair.
Connection between Tumor Suppressor BRCA1 and PTEN in Damaged DNA Repair.
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DOI：
10.3389/fonc.2014.00318
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发表时间：
2014
影响因子：
4.7
通讯作者：
Matsuda S
中科院分区：
文献类型：
--
作者：
Minami A;Nakanishi A;Ogura Y;Kitagishi Y;Matsuda S
基因组的不稳定最终导致细胞死亡或凋亡。肿瘤抑制因子10号染色体上的磷酸酶和张力蛋白同源物（PTEN）是一种双特异性磷酸酶，具有蛋白磷酸酶活性和脂质磷酸酶活性，可拮抗PI 3 K活性。缺乏PTEN的细胞具有组成性更高水平的PIP 3和激活的下游PI 3 K/AKT靶。BRCA 1是一种著名的乳腺癌抑癌基因，与乳腺癌的发病风险和遗传易感性有关。许多研究表明，PTEN和BRCA 1在DNA损伤反应中起着关键作用。BRCA 1在功能上与PTEN合作，可能是几种肿瘤发展中的重要阻断。事实上，PTEN和BRCA 1基因被认为是许多人类癌症中最常见的缺失和/或突变基因之一。PI 3 K/AKT通路在BRCA 1缺陷型人类癌细胞中具有组成性活性。这些PTEN或BRCA 1功能的缺失或降低，无论是突变还是表达减少，在各种肿瘤的发展中起作用。本文综述了BRCA 1和PTEN在基因组稳定性和癌细胞信号转导中的作用。
Genomic instability finally induces cell death or apoptosis. The tumor suppressor, phosphatase and tensin homolog on chromosome 10 (PTEN), is a dual-specificity phosphatase, which has protein phosphatase activity and lipid phosphatase activity that antagonizes PI3K activity. Cells that lack PTEN have constitutively higher levels of PIP3 and activated downstream PI3K/AKT targets. BRCA1, a well-known breast cancer tumor suppressor, is to associate with breast cancer risk and genetic susceptibility. Many studies have demonstrated that PTEN, as well as BRCA1, plays a critical role in DNA damage responses. The BRCA1 functionally cooperates with PTEN and might be an essential blockage in the development of several tumors. Actually, the PTEN and BRCA1 genes are recognized as one of the most frequently deleted and/or mutated in many human cancers. The PI3K/AKT pathway is constitutively active in BRCA1-defective human cancer cells. Loss or decrease of these PTEN or BRCA1 function, by either mutation or reduced expression, has a role in various tumor developments. This review summarizes recent findings of the function of BRCA1 and PTEN involved in genomic stability and cancer cell signaling.