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.
Nogueira
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Departamento de Química, Disciplina de Bioquímica, Instituto de Biociências, Universidade Estadual Paulista, Botucatú, São Paulo, Brazil.
Brentani
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D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D007527:Isoenzymes; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011988:Receptors, Thyroid Hormone; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D014284:Triiodothyronine; D013629:Tamoxifen; D004958:Estradiol; D005993:Glycerolphosphate Dehydrogenase; D007770:L-Lactate Dehydrogenase