Effects of Estradiol on Deoxyribonucleic Acid Polymerase α Activity in the Ishikawa Human Endometrial Adenocarcinoma Cell Line*

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Abstract
The effects of estradiol on DNA polymerase α activity were investigated in an estrogen-responsive human endometrial cancer cell line (Ishikawa) derived from a well differentiated endometrial adenocarcinoma. These cells are known to respond to estradiol by increasing progesterone receptor levels, alkaline phosphatase activity, and cell density. Four- to 5-fold increases in DNA polymerase α activity occurred when estradiol was added to cultures of Ishikawa cells in medium containing charcoal-treated fetal bovine serum. Maximal stimulation was achieved at 18 h during incubations with 10−8 M estradiol, but significant effects also were found with 10−9 and 10 −6M. These effects were almost completely counteracted by a 100-fold excess of 4-hydroxytamoxifen. At 10−6 M, the antiestrogen hadno influence on the basal levels of DNA polymerase α. Medroxyprogesterone acetate (10−6 M) was ineffective as either an enhancer of enzymatic activity or an antiestrogen when tested in combination with 10−8 M estradiol, even in the presence of appreciable levels of specific progesterone binders. The responsiveness of the Ishikawa cells to estrogen contrasts with the lack of effects of estradiol on DNA polymerase α activity in another human endometrial adenocarcinoma cell line (HEC-50).

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