ESTROGEN ACTION IN TARGET-CELLS - SELECTIVE REQUIREMENTS FOR ACTIVATION OF DIFFERENT HORMONE RESPONSE ELEMENTS

RENE1 cells, an estrogen receptor positive rat uterine endometrial cel l line immortalized with the E1A oncogene, were analyzed for the prese nce of estrogen-dependent signal transduction pathways using the induc tion of transfected as well as endogenous genes. RENE1 cells express t he 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 consensu s estrogen response element (ERE) in transient transfection assays and alterations in endogenous transcripts visualized by utilizing differe ntial display methodology. However, neither transfected reporter const ructs 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 induce d by estrogens in the uterus in vivo. In addition, estradiol did not i nduce endogenous c-fos expression or the activity of CAT reporters con taining the c-fos ERE in a stable transfectant of RENE1 cells with a 3 -fold elevation in estrogen receptor content. Under identical conditio ns, TPA and serum rapidly induce c-fos transcription in RENE1 cells, i ndicating that the lack of inducibility by estradiol is not due to a g eneral inhibitor of transcription of these genes. These results sugges t that RENE1 cells lack factors present in normal uterine cells which are required for the estrogenic induction of a specific subset(s) of E REs. These observations support the generally evolving hypothesis that steroid hormones may act through composite response elements via inte ractions with other transcription factors, in addition to functioning as homodimers at classical palindromic response elements.