Antiestrogens stimulate expression of transiently transfected and endogenous genes in rat pituitary tumor cell lines.
Tamoxifen, nafoxidine, and clomiphene (1 x 10(-5) M) cause 5- to 15-fold increases in transient expression of plasmids transfected into rat somatomammotrophic pituitary tumor cell lines. To be effective, the antiestrogen must be present during the calcium phosphate transfection though it does not enhance the nuclear uptake or stability of transfected plasmid. The effect occurs with mammalian (rat growth hormone, mouse metallothionein I) or viral (thymidine kinase, Rous sarcoma virus) promoters and is inhibited by prior exposure of cells to high concentrations of estradiol but not glucocorticoid, progesterone or testosterone. Cis-tamoxifen, a conformation with much lower affinity for the estrogen receptor, has only one-fifth the effect of tamoxifen. Neither estradiol nor diethylstilbestrol have similar effects. Tamoxifen also increases endogenous rat growth hormone mRNA in these pituitary tumor cell lines. Transient expression in a number of other cell lines (JEG-3, COS-7, PC-12) is unaffected by tamoxifen suggesting the effect may be cell-type specific though MCF-7 cells are slightly responsive. The mechanism for the potent stimulation of gene transcription by these agents is not apparent but may be relevant to the mechanism of action of these agents as estrogen antagonists in vivo.
Larsen
P R
PR
Howard Hughes Medical Institute Laboratory, Brigham and Women's Hospital, Boston, MA.
Warne
R
R
D000818:Animals; D015139:Blotting, Southern; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000235:genetics; D009154:Mutation; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D013629:Tamoxifen; D013006:Growth Hormone