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纸质出版:2013
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王杨,陈彬,姜晓梅,王越,付晓红,何凤田.睾酮对乳腺癌细胞中FEN1表达的影响[J].陆军军医大学学报(原第三军医大学学报),2013,35(02):95-98.
Wang Yang,Chen Bin,Jiang Xiaomei,Wang Yue,Fu Xiaohong,He Fengtian.Effect of testosterone on FEN1 expression in breast cancer cells[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(02):95-98.
目的 探讨睾酮(testosterone,T)在乳腺癌细胞中对瓣状核酸内切酶(flap endonuclease 1,FEN1)表达的影响及其机制。 方法 以MCF-7作为研究对象,采用RT-PCR观察雌二醇(17β-estradiol,E2)单独作用以及分别与雌激素受体(estrogen receptor,ER)拮抗剂ICI182,780(ICI)和MAPK途径抑制剂U0126共同作用时FEN1表达的变化。以MCF-7aro(芳香化酶过表达的MCF-7)作为研究对象,采用RT-PCR观察加入单独的睾酮以及睾酮和芳香化酶抑制剂来曲唑(letrozole)共同作用时FEN1表达的变化;采用Western blot观察睾酮单独作用以及分别与来曲唑和U0126共同作用时FEN1、p-ERK和p-Elk的变化。 结果 与对照组比较,加入雌二醇后MCF-7细胞中FEN1 mRNA的表达升高2.04倍(P0.01),加入ICI和U0126后分别降低10.63倍和2.17倍(P0.01)。加入睾酮后MCF-7aro细胞中FEN1 mRNA的表达升高1.66倍(P0.01),蛋白的表达升高1.80倍(P0.01);加入来曲唑后FEN1 mRNA的表达下降2.38倍,蛋白的表达降低1.84倍,加入U0126后蛋白的表达降低2.28倍(P0.01);加入睾酮后ERK和Elk-1的磷酸化水平分别升高2.28倍和2.60倍(P0.01),加入来曲唑后ERK和Elk-1的磷酸化水平分别降低2.60倍和2.37倍(P0.01),加入U0126后ERK和Elk-1的磷酸化水平分别降低10.38倍和119.50倍(P0.01)。 结论 睾酮可通过MAPK途径上调MCF-7 aro细胞中FEN1的表达。
Objective To determine the effect of testosterone on the expression of flap endonuclease 1 (FEN1) in breast cancer. Methods The expression of FEN1 in MCF-7 cells was observed by RT-PCR after the cells were treated with 17β-estradiol (E2)
E2 combined with ICI182
780
an estrogen receptor antagonist
and E2 combined with U0126
a MEK inhibitor
respectively. In MCF-7 cells over-expressing aromatase (MCF-7/Aro)
the expression of FEN1 was observed by RT-PCR when cells were treated with testerone or testerone combined with letrozole
one of aromatase inhibitors. The expression of FEN1 protein
p-ERK and p-Elk was observed by Western blotting when the cells were treated with testosterone
testosterone combined with letrozole
or combined with U0126. Results In MCF-7 cells
E2 resulted in an increase in the expression of FEN1 mRNA by 2.04 folds (P0.01)
which was inhibited by ICI182
780 or U0126 (10.63 and 2.17 folds
P0.01). In MCF-7aro cells
testosterone resulted in an increase in the expression of FEN1 at mRNA and protein levels by 1.66 and 1.80 folds respectively(P0.01)
which was inhibited by letrozole (2.38 and 1.84 folds
P0.01) or U0126(2.28 folds for protein only
P0.01). Testosterone increased the phosphorylation of p-ERK and p-Elk by 2.28 and 2.60 folds
which was inhibited by letrozole by 10.38 folds or U0126 by 119.50 folds(P0.01). Conclusion Testosterone up-regulates FEN1 in MCF-7aro cells through MAPK signaling pathway.
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