Estrogen-induced anchorage-independence in human endometrial stromal cells.
Estrogens are important etiologic agents for most gynecologic malignancies, and chronic exposure to estrogen that is unopposed by progestins conveys the greatest risk. Treatments with estrogen facilitate the process of malignant transformation in rodents, but relatively few studies of estrogen-induced carcinogenesis have been performed using human cells. Most malignancies in estrogen-responsive tissues arise from epithelial cells, but an increasing body of evidence emphasizes the role of stromal cells as mediators of the effects of estrogens on epithelial 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. Acute treatments with the estrogens diethylstilbestrol (DES), 17 beta-estradiol (E2) and beta-dienestrol enhance anchorage-independent proliferation (AIP) of SV40-immortalized human endometrial stromal cells in the rank order of DES > E2 > beta-dienestrol. The anti-estrogenic compound tamoxifen inhibits DES-induced AIP. The magnitude of DES-induced AIP increases with prolonged duration of treatment. After 11 months of chronic treatment with 0.1 nM DES, AIP was 20-fold higher than in vehicle-treated control cultures. Expression of the estrogen receptor was altered by treatments with DES in parallel with increased capacity for AIP. These conditionally immortal human endometrial stromal cells appear to be a good model for estrogen-induced transformation of human cells.
Xu
L H
LH
Department of Pathology, University of North Carolina at Chapel Hill 27599-7525, USA.
Rinehart
C A
CA
Kaufman
D G
DG
D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000139:chemically induced; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000009:adverse effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D017154:Stromal Cells / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen