Role of estrogen and progesterone in the survival of ovarian tumors--a study of the human ovarian adenocarcinoma cell line OC-117-VGH.
BACKGROUND
The role of estrogen and progesterone in ovarian carcinogenesis and the growth and survival of ovarian cancer cells is controversial. In this study, we tested the effects of various concentrations of estrogen and progesterone on the survival of an ovarian cancer cell line.


METHODS
The ovarian adenocarcinoma cell line, OC-117-VGH, is deficient in the following receptors: estrogen receptor (ER)alpha, ERbeta, and progesterone receptor (PR). Serial concentrations of estrogen and progesterone were used to evaluate the effects of estrogen and progesterone on the survival of ovarian cancer cells. The apoptosis-related genes Bcl-2 and Bax were used to check the possible mechanism of an estrogen or progesterone effect on survival of the cancer cell line.


RESULTS
Estrogen 0.01-1.0 microM and progesterone 0.1-10.0 microM affected cell survival. As predicted, progesterone successfully downregulated anti-apoptotic Bcl-2 expression, and dose-dependently suppressed Bcl-2 expression in tumor cells. Paradoxically, estrogen showed the same effects. In addition, both hormones downregulated proapoptotic Bax expression. The net effect confirmed the role of downregulated Bcl-2 in reducing the survival of ovarian cancer cells.


CONCLUSIONS
Based on the findings of decreased survival and/or growth in OC-117-VGH ovarian adenocarcinoma cells treated with either estrogen or progesterone, we suspect that both hormones act effectively against ER-negative and PR-negative ovarian cancer cells. These findings should lead to a reassessment of hormone therapy for ovarian cancers.
Chao
Kung-Chong
KC
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan. kcchao@vghtpe.gov.tw
Wang
Peng-Hui
PH
Yen
Ming-Shyen
MS
Chang
Chi-Ching
CC
Chi
Chin-Wen
CW
D000230:Adenocarcinoma / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011374:Progesterone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011374:Progesterone