Multihormone regulation of MMTV-LTR in transfected T-47-D human breast cancer cells.
Multihormonal regulation on the long terminal repeat (LTR) region of mouse mammary tumour virus (MMTV) has been studied using T-47-D human breast cancer cells stably transfected with the steroid sensitive LTR-C3 chimaeric gene. The specificity of steroid action on transfected LTR sequences has been compared with regulation of endogenous cellular markers. We conclude that the hormone response element of the LTR can be induced by physiological concentrations of androgen, progestin and glucocorticoid. 17 beta-Oestradiol did not regulate the LTR at physiological levels but an effect was found at 10(-6) M. This effect was not inhibited by antioestrogen nor was it reproduced by the synthetic oestrogen diethylstilboestrol suggesting such effects do not occur via the oestrogen receptor. The antioestrogens tamoxifen and transhydroxytamoxifen do not induce the LTR. No significant steroid competition was found in LTR regulation: whilst oestradiol did not act at physiological concentration it did not interfere with induction by androgen, progestin or glucocorticoid. Such gene regulation did not simply follow receptor status of the cells nor was it reflected in patterns of growth regulation by steroids. The implications of these findings on the mechanism of steroid hormone action are discussed.
Glover
J F
JF
Laboratory of Cellular Endocrinology, Imperial Cancer Research Fund, London, England.
Darbre
P D
PD
D001943:Breast Neoplasms / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005819:Genetic Markers; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D010957:Plasmids; D011397:Promegestone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D006728:Hormones; D013629:Tamoxifen; D013739:Testosterone; D004958:Estradiol; D004054:Diethylstilbestrol; D003907:Dexamethasone; D011397:Promegestone