The relationship between estrogen and genes in the molecular pathogenesis of endometrial carcinoma.
The relationship between estrogen and genes in the molecular pathogenesis of endometrial carcinoma.
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子宫内膜癌分子发病机制中雌激素与基因的关系。
DOI：
10.1007/s13669-013-0074-3
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Katabuchi H.
中科院分区：
文献类型：
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作者：
Tashiro H;Katabuchi H.
子宫内膜癌是女性生殖系统常见的恶性肿瘤。它包括一种常见的雌激素依赖性类性腺癌（EC）的绝经期和绝经后妇女和一种罕见的雌激素非依赖性浆液性癌的老年妇女。EC表现出特定的突变（例如，但激素和基因变化之间的联系仍不清楚。众所周知，EC的一个子集具有改变的DNA错配修复（MMR）系统，导致微卫星不稳定性。最近，DNA聚合酶ε的催化亚基（POLE），其在DNA碱基切除修复（BER）系统中针对突变（例如，通过雌激素代谢物），显示在EC的一小部分中突变，表现出微卫星稳定性。这表明MMR或BER系统中的缺陷提供了实现基因组不稳定性的替代机制，导致获得特定基因突变。一种用于解决雌激素在PTEN突变细胞中的作用的模型小鼠显示，雌激素使PTEN突变细胞与其子宫内膜中的周围细胞一起克隆增殖，并且雌激素的消耗诱导具有雌激素非依赖性能力的PTEN突变细胞的优势生长，导致瘤形成。总之，这些机制可以解释为什么EC的发病率随着绝经后或绝经后状态而增加。
Endometrial carcinoma is a common cancer of the female reproductive system. It comprises a common estrogen-dependent endometrioid carcinoma (EC) in peri- and postmenopausal women and an uncommon estrogen-independent serous carcinoma in older women. ECs exhibit specific mutations (e.g., in PTEN gene), but the link between hormones and genetic changes remains unclear. A subset of ECs is well known to possess an altered DNA mismatch repair (MMR) system, causing microsatellite instability. Recently, the catalytic subunit of DNA polymerase ε (POLE), which functions in the DNA base excision repair (BER) system against mutations (e.g., by estrogen metabolite), was shown to be mutated in a small subset of ECs, exhibiting microsatellite stability. This suggests that a defect in either MMR or BER system provides alternative mechanisms to achieve genomic instability, resulting in acquisition of specific gene mutations. A model mouse for addressing the effect of estrogen in PTEN-mutated cells showed that estrogen clonally proliferates PTEN-mutated cells together with surrounding cells in its endometrium, and depletion of estrogen induces predominant growth of PTEN-mutated cells with estrogen-independent capabilities, resulting in neoplasia. Taken together, those mechanisms may explain why the incidence of ECs increases with peri- or post-menopausal status.