Estrogen regulates DNA methyltransferase 3B expression in Ishikawa endometrial adenocarcinoma cells.
It is well-known that exposure to unopposed estrogen is considered as an important risk factor for endometrial cancer. Recent studies have shown that over-expression of DNA methyltransferases (DNMTs) are involved in the development of endometrial cancer. Therefore, the present study was undertaken to elucidate the impact of estrogen on the expression of DNMTs in endometrial cancer. Ishikawa cell line was used. Flow cytometry analysis demonstrated that 17 beta-estradiol (E(2)) enhanced the cell proliferation with a peak at 10(-8) M. Over-expression of DNMT3B treated with E(2) was confirmed by real-time PCR and western blotting analysis. Furthermore, the up-regulation of DNMT3B expression induced by E(2) was suppressed by the addition of ICI182780. However, we did not observe changes in the expression of DNMT1. Our study suggests that estrogen up-regulating the expression of DNMT3B in an ER-dependent pathway may be a possible mechanism for estrogen facilitates the malignant transformation of endometrial cancer cells.
Cui
Min
M
Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, Shandong, People's Republic of China.
Wen
Zeqing
Z
Yang
Zhongli
Z
Chen
Ji
J
Wang
Fei
F
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000704:Analysis of Variance; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D000097584:DNA Methyltransferase 3B
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D004958:Estradiol; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000619380:DNMT1 protein, human