共济失调毛细血管扩张症致病基因与乳腺癌易感性

Ataxia-telangiectasia mutated gene and breast cancer susceptibility

摘要:

乳腺癌是与环境因素密切相关的肿瘤之一，致癌因素诱发的DNA损伤信号被传送到多个效应因子，最终导致细胞坏死和癌变。其中，共济失调性毛细血管扩张症致病基因 (Ataxia-telangiectasia mutated, ATM) 编码的ATM蛋白激酶是DNA损伤应答的主要调控因子，其通过磷酸化一系列下游底物来应对DNA损伤，这在抑制乳腺癌的发生发展中起到了重要的作用。ATM基因突变后，导致损伤DNA不能得到正确修复，最终加速了乳腺癌的转化和增殖。随着对ATM基因结构、功能及乳腺癌易感性机制研究的深入，ATM基因与乳腺癌易感性关系已引起广泛的重视。以下就ATM基因突变、多态性和甲基化等几个方面与乳腺癌易感性的关系进行了简要概述。

Abstract:

Breast cancer is bound up with the environment. As a consequence of DNA damage induced by environmental carcinogens, a number of sophisticated sensing and transduction systems are initiated and the signal is conveyed simultaneously to multiple effectors. This process ultimately results in cancer. The protein kinase ATM that encoded by ATM (Ataxia-telangiectasia mutated) gene is the master regulator of DNA damage response. In this consecutive reaction, the protein kinase ATM responds to the DNA damage by phosphorylating a variety of downstream substrates, which plays an important role in the inhibition of the development of breast cancer. After ATM gene mutate, DNA damaged could not be accurately repaired and finally accelerates breast cancer transformation and proliferation. With the further research of ATM gene structure, function and breast cancer susceptibility, the extensive attention is paid to the relationship between ATM gene and breast cancer susceptibility. We reviewed the research advances in breast cancer susceptibility in several aspects of ATM gene, including mutation, polymorphism and methylation.