Estrogen signaling and the DNA damage response in hormone dependent breast cancers.
Estrogen signaling and the DNA damage response in hormone dependent breast cancers.
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DOI：
10.3389/fonc.2014.00106
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发表时间：
2014
影响因子：
4.7
通讯作者：
Caldon CE
中科院分区：
文献类型：
--
作者：
Caldon CE
雌激素是乳腺组织正常生长发育所必需的，但高水平的雌激素是乳腺癌的主要危险因素。雌激素可能导致乳腺癌的一种机制是通过诱导DNA损伤。该观点讨论了雌激素通过调节关键效应蛋白（包括ATM，ATR，CHK1，BRCA1和p53）以及这些蛋白对雌激素受体信号传导的反馈来改变DNA损伤反应（DDR）和DNA修复的机制。我们提出了这样的假设，即雌激素受体信号传导会聚到抑制有效的DNA修复和凋亡，有利于增殖。这在雌激素依赖性乳腺癌中很重要，因为它会影响雌激素诱导的DNA损伤以及其他遗传毒性损伤的处理。DDR和DNA修复蛋白在雌激素反应性乳腺癌中经常发生突变或改变，这将进一步改变DNA损伤的过程。最后，雌激素信号传导对DNA损伤的作用也与治疗环境相关，因为雌激素对DDR的抑制有可能改变癌症对诱导DNA损伤的抗激素治疗或化疗的反应。
Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR) and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1, and p53 and the feedback on estrogen receptor signaling from these proteins. We put forward the hypothesis that estrogen receptor signaling converges to suppress effective DNA repair and apoptosis in favor of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer, which will further change the processing of DNA damage. Finally, the action of estrogen signaling on DNA damage is also relevant to the therapeutic setting as the suppression of a DDR by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.