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Título: | Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells |
Autor: | González-Sancho, José Manuel CSIC ORCID; Figueroa, Angélica CSIC ORCID; López-Barahona, Mónica; López, Eva CSIC; Beug, H.; Muñoz Terol, Alberto CSIC ORCID | Fecha de publicación: | 2002 | Editor: | Wiley-Blackwell | Citación: | Molecular Carcinogenesis 34(1): 25-34 (2002) | Resumen: | The relationship between thyroid hormone (triiodothyronine, T3) and breast cancer is unclear. We studied the effect of the c-erbA/TRα proto-oncogene encoding a functional T3 receptor (TRα1), of its ligand T3, and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacity of nontumorigenic mammary epithelial cells (EpH4). We found that EpH4 cells expressing ectopically TR (EpH4 + TRα1) orv-erbA (EpH4 + v-erbA) proliferated faster than parental EpH4 cells that contained low levels of endogenous TR. T3 inhibited DNA synthesis and proliferation in EpH4 + TRα1 cells but not EpH4 or EpH4 + v-erbA cells. The study of cell-cycle genes showed that T3 decreased cyclin D1 RNA and protein levels in EpH4 + TRα1 cells. In addition, T3 downregulated the expression of T1, a gene that is overexpressed in human breast adenocarcinomas and is induced by mitogens, serum, and several oncogenes and cytokines. Inhibition of the T1 gene by T3 required both de novo mRNA and protein synthesis. Furthermore, T3 abolished the induction of T1 by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and inhibited the activity of an activation protein 1-dependent promoter (-73-Col-CAT) in EpH4 + TRα1 cells, suggesting that interference with activation protein 1 transcription factor plays a part in the inhibition of the T1 gene. Our results showed that T3 reduced the proliferation of mammary epithelial cells and inhibited the expression of cyclin D1 and T1 genes. © 2002 Wiley-Liss, Inc. | URI: | http://hdl.handle.net/10261/80079 | DOI: | 10.1002/mc.10046 | Identificadores: | doi: 10.1002/mc.10046 issn: 0899-1987 e-issn: 1098-2744 |
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