Estrogen action in target cells: selective requirements for activation of different hormone response elements.
RENE1 cells, an estrogen receptor positive rat uterine endometrial cell line immortalized with the E1A oncogene, were analyzed for the presence of estrogen-dependent signal transduction pathways using the induction of transfected as well as endogenous genes. RENE1 cells express the estrogen receptor as analyzed by Northern blots and ligand binding assays (40 fmoles/mg protein). The receptor system appears functional, based on the induction of reporter constructs containing the consensus estrogen response element (ERE) in transient transfection assays and alterations in endogenous transcripts visualized by utilizing differential display methodology. However, neither transfected repoter constructs containing the c-fos ERE, nor the endogenous c-fos, c-jun, or c-myc genes are induced by estrogens in these cells despite being induced by estrogens in the uterus in vivo. In addition, estradiol did not induce endogenous c-fos expression or the activity of CAT reporters containing the c-fos ERE in a stable transfectant of RENE1 cells with a 3-fold elevation in estrogen receptor content. Under identical conditions, TPA and serum rapidly induce c-fos transcription in RENE1 cells, indicating that the lack of inducibility by estradiol is not due to a general inhibitor of transcription of these genes. These results suggest that RENE1 cells lack factors present in normal uterine cells which are required for the estrogenic induction of a specific subset(s) of EREs. These observations support the generally evolving hypothesis that steroid hormones may act through composite response elements via interactions with other transcription factors, in addition to functioning as homodimers at classical palindromic response elements.
Hyder
S M
SM
Department of Pharmacology, University of Texas Medical School, Houston 77225, USA.
Shipley
G L
GL
Stancel
G M
GM
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001769:Blood; D015152:Blotting, Northern; D002460:Cell Line; D002461:Cell Line, Transformed; D004247:DNA / Q000187:drug effects; D004717:Endometrium / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D016762:Genes, fos / Q000235:genetics; D008969:Molecular Sequence Data; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D017500:Adenovirus E1A Proteins; D011960:Receptors, Estrogen; D004958:Estradiol; D004247:DNA; D013755:Tetradecanoylphorbol Acetate