4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells
4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells
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DOI：
10.1016/j.mce.2014.10.027
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发表时间：
2015-01-15
影响因子：
4.1
通讯作者：
Shiozawa, Tanri
中科院分区：
文献类型：
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作者：
Ke, He;Suzuki, Akihisa;Shiozawa, Tanri
邻苯二酚雌激素，例如4-羟基雌二醇（4-OHE 2），是形成DNA加合物的雌激素代谢物，可能会诱导乳腺细胞突变和随后的细胞转化;然而，人们对它们在子宫内膜致癌作用中的作用知之甚少。此外，目前还不清楚4-OHE 2是否能够诱导参与致癌作用的特定基因的DNA损伤或“前”突变状态，如微卫星不稳定性（MSI）。因此，我们修改了末端转移酶依赖PCR的应用毛细管测序仪检测DNA损伤在单碱基水平。利用这种方法，我们证明了4-OHE 2直接诱导子宫内膜癌中PTEN第5外显子的密码子130/131的DNA损伤，这是PTEN突变的热点。而雌二醇和4-OHE 2处理对永生化子宫内膜腺细胞的MSI状态无影响。4-OHE 2可能通过诱导PTEN基因130/131位密码子突变而参与子宫内膜癌的发生。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Catechol estrogens, such as 4-hydroxyestradiol (4-OHE2), are estrogen metabolites that form DNA adducts and may induce mutations and subsequent cell transformation in mammary cells; however, little is known about their roles in endometrial carcinogenesis. Furthermore, it remains unclear whether 4-OHE2 is able to induce DNA damage on specific genes involved in carcinogenesis or a 'pro'-mutation status such as microsatellite instability (MSI). Therefore, we modified terminal transferase-dependent PCR by the application of a capillary sequencer to detect DNA damage at the single base level. Using this method, we demonstrated that 4-OHE2 directly induced DNA damage on codon 130/131 in exon 5 of PTEN, which is a mutation hot spot for PTEN in endometrial carcinoma. Whereas, both estradiol and 4-OHE2 treatment did not affect MSI status in immortalized endometrial glandular cells. 4-OHE2 might contribute to endometrial carcinogenesis by inducing PTEN mutation on codon 130/131. (C) 2014 Elsevier Ireland Ltd. All rights reserved.