Stimulatory effect of estrogen on the growth of endometrial cancer cells is regulated by cell-cycle regulators.
Estrogen is known as a major risk factor in tumorigenesis of the endometrium. The aim of this study is to establish stable estrogen-responsive endometrial cancer cell lines and to investigate the mechanism of estrogen action, focusing on cell-cycle regulation. Human wild-type estrogen receptor cDNA was transfected into endometrial cancer cells (Ishikawa) and estrogen-responsive cell lines were cloned. Their estrogen responsiveness was evaluated by the effect of estrogen on cellular growth and progesterone receptor expression. It was quantitatively estimated by immunocytochemistry or immunoblotting how the expression of cell-cycle regulators such as cyclin D1, cyclin E, Cyclin A, p53, p21 and p27 was regulated by estrogen. A cell line stably responsive to estrogen was established, and cells proliferated and the glandular structure was formed by estrogen stimulation. Cyclin D1 expression increased at 6-24h and cyclin A gradually increased until 48h of estrogen treatment compared with untreated cells. On the other hand, p53 and p21 expressions decreased at 6-24h, and p27 gradually decreased until 24h by estrogen. Our results show that the stimulatory effect of estrogen on cell proliferation may be regulated by the up-regulation of cyclin D1 and cyclin A, and down-regulation of p53, p21 and p27. This cell line is useful to clarify the molecular mechanism of estrogen action on endometrial cancer.
Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. watajun@med.kitasato-u.ac.jp
Jun
J
Watanabe
Yuko
Y
Kamata
Norihisa
N
Seo
Isao
I
Okayasu
Hiroyuki
H
Kuramoto
D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans
D047628:Estrogen Receptor alpha; D004958:Estradiol