Triiodothyronine mimics the effects of estrogen in breast cancer cell lines

MCF-7 (estrogen receptor positive--ER+) and MDA-MB-231 (estrogen receptor negative--ER-) are human breast cancer cell lines which express functional thyroid hormone receptors (c-erb A alpha1 and c-erb beta1) as indicated by stimulation of mitochondrial alpha-glycerophosphate dehydrogenase. In MCF-7, mimicking E2, T3 stimulated growth in a dose-dependent (10(10) M - 10(-8) M) manner, induced the expression of progesterone receptor and growth factor TGFalpha mRNAs and inhibited that of TGFbeta mRNA; T3 also increased progesterone binding and LDH5 isozyme activities. None of these effects were observed in (ER-) MDA-MB-231 cells. 10(-6) M tamoxifen (TAM) reverted growth stimulation, suppressed progesterone receptor and TGFalpha mRNA induction and restored TGFbeta mRNA to control levels in T3-treated MCF-7 cells. That T3 is acting in MCF-7 cells via its binding to ER is suggested by the immunoprecipitation of pre-bound 125I-T3 from MCF-7 nuclear extracts by an ER-specific monoclonal antibody and by the displacement of 3H-estradiol binding to ER by radioinert T3.