Hormone-induced DNA damage response and repair mediated by cyclin D1 in breast and prostate cancer.
Hormone-induced DNA damage response and repair mediated by cyclin D1 in breast and prostate cancer.
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DOI：
10.18632/oncotarget.19413
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发表时间：
2017-10-10
期刊：
影响因子：
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通讯作者：
Pestell RG
中科院分区：
文献类型：
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作者：
Di Sante G;Di Rocco A;Pupo C;Casimiro MC;Pestell RG
细胞周期控制蛋白控制导致产生两个相同子细胞的事件。通过一系列检查点协商不同的连续时间阶段，间隙1（G1）、间隙0（G 0）、合成（S）、间隙2（G2）和有丝分裂（M），在此期间，在复制DNA之前评估局部细胞环境的可复制性。细胞周期蛋白D1是全酶的一个关键调节亚基，通过磷酸化pRB蛋白促进G1/S-相转变。细胞周期蛋白D1过表达被认为是几种类型癌症的驱动力，cdk抑制剂在临床上被有效地用于治疗ERα+乳腺癌。基因组DNA受到电离辐射、化学致癌物和细胞代谢产生的活性氧（ROS）的破坏。此外，包括雌激素和雄激素在内的特定激素控制着损伤DNA的途径。DNA损伤反应（DDR）途径的缺陷可导致基因组不稳定和癌症。有证据表明，细胞周期蛋白D1结合参与DNA修复的蛋白质，包括BRCA 1，RAD 51，BRCA 2，并参与DNA损伤和DNA修复过程。由于细胞周期蛋白D1对DNA损伤的修复具有重要的作用，且细胞周期蛋白D1依赖性激酶活性的抑制剂已被应用于临床，本文综述了细胞周期蛋白D1在介导DDR（包括雌激素和雄激素诱导的DDR）中的作用。
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein. Cyclin D1 overexpression is considered a driving force in several types of cancers and cdk inhibitors are being used effectively in the clinic for treatment of ERα+ breast cancer. Genomic DNA is assaulted by damaging ionizing radiation, chemical carcinogens, and reactive oxygen species (ROS) which are generated by cellular metabolism. Furthermore, specific hormones including estrogens and androgens govern pathways that damage DNA. Defects in the DNA Damage Response (DDR) pathway can lead to genomic instability and cancer. Evidence is emerging that cyclin D1 bind proteins involved in DNA repair including BRCA1, RAD51, BRCA2 and is involved in the DNA damage and DNA repair processes. Because the repair of damaged DNA appears to be an important and unexpected role for cyclin D1, and inhibitors of cyclin D1-dependent kinase activity are being used in the clinic, the latest findings on the role of cyclin D1 in mediating the DDR including the DDR induced by the hormones estrogen and androgen is reviewed.