ESTROGEN-INDUCED ANCHORAGE-INDEPENDENCE IN HUMAN ENDOMETRIAL STROMAL CELLS

Estrogens are important etiologic agents for most gynecologic malignan cies, and chronic exposure to estrogen that is unopposed by progestins conveys the greatest risk. Treatments with estrogen facilitate the pr ocess of malignant transformation in rodents, but relatively few studi es of estrogen-induced carcinogenesis have been performed using human cells. Most malignancies in estrogen-responsive tissues arise from epi thelial cells, but an increasing body of evidence emphasizes the role of stromal cells as mediators of the effects of estrogens on epithelia l cells. Our studies were designed to assess estrogens as carcinogens for human endometrial stromal cells and to provide a basis for studies of the role of stroma in estrogen-induced carcinogenesis in humans, A cute treatments with the estrogens diethylstilbestrol (DES), (17)beta- estradiol (E(2)) and beta-dienestrol enhance anchorage-independent pro liferation (AIP) of SV40-immortalized human endometrial stromal cells in the rank order of DES > E(2) > beta-dienestrol. The anti-estrogenic compound tamoxifen inhibits DES-induced AIP. The magnitude of DES-ind uced AIP increases with prolonged duration of treatment. After 11 mont hs of chronic treatment with 0.1 nM DES, AIP was 20-fold higher than i n vehicle-treated control cultures. Expression of the estrogen recepto r was altered by treatments with DES in parallel with increased capaci ty for AIP. These conditionally immortal human endometrial stromal cel ls appear to be a good model for estrogen-induced transformation of hu man cells. (C) 1995 Wiley-Liss, Inc.