The Thyroid Hormone Receptor Is a Suppressor of ras-Mediated Transcription, Proliferation, and Transformation

@article{citeulike:2272907, abstract = {The thyroid hormone triiodothyronine (T3) has a profound effect on growth, differentiation, and metabolism in higher organisms. Here we demonstrate that T3 inhibits ras-induced proliferation in neuroblastoma cells and blocks induction of cyclin D1 expression by the oncogene. The hormone, at physiological concentrations, strongly antagonizes the transcriptional response mediated by the Ras/mitogen-activated protein kinase/ribosomal-S6 subunit kinase (Rsk) signaling pathway in cells expressing thyroid hormone receptors (TRs). T3 blocks the response to the oncogenic forms of the three ras isoforms (H-, K-, and N-ras) and both TR{alpha} and TR{beta} can mediate this action. The main target for induction of cyclin D1 transcription by oncogenic ras in neuroblastoma cells is a cyclic AMP response element (CRE) located in proximal promoter sequences, and T3 represses the transcriptional activity of b-Zip transcription factors such as CREB (CRE-binding protein) or ATF-2 (activation transcription factor 2) that are direct targets of Rsk2 and bind to this sequence. The hormone also blocks fibroblast transformation by oncogenic ras when TR is expressed. Furthermore, TRs act as suppressors of tumor formation by the oncogene in vivo in nude mice. The TR{beta} isoform has stronger antitransforming properties than the {alpha} isoform and can inhibit tumorigenesis even in hypothyroid mice. These results show the existence of a previously unrecognized transcriptional cross talk between the TRs and the ras oncogene which influences relevant processes such as cell proliferation, transformation, or tumorigenesis. 10.1128/MCB.24.17.7514-7523.2004}, author = {Garcia-Silva, Susana and Aranda, Ana }, citeulike-article-id = {2272907}, doi = {http://dx.doi.org/10.1128/MCB.24.17.7514-7523.2004}, journal = {Mol. Cell. Biol.}, keywords = {hormone, nuclear, ras, receptor, regulation, thr, thyroid, transcription}, month = {September}, number = {17}, pages = {7514--7523}, posted-at = {2008-01-22 10:19:55}, priority = {5}, title = {The Thyroid Hormone Receptor Is a Suppressor of ras-Mediated Transcription, Proliferation, and Transformation}, url = {http://dx.doi.org/10.1128/MCB.24.17.7514-7523.2004}, volume = {24}, year = {2004} }

TY - JOUR ID - citeulike:2272907 L3 - citeulike-article-id:2272907 N2 - The thyroid hormone triiodothyronine (T3) has a profound effect on growth, differentiation, and metabolism in higher organisms. Here we demonstrate that T3 inhibits ras-induced proliferation in neuroblastoma cells and blocks induction of cyclin D1 expression by the oncogene. The hormone, at physiological concentrations, strongly antagonizes the transcriptional response mediated by the Ras/mitogen-activated protein kinase/ribosomal-S6 subunit kinase (Rsk) signaling pathway in cells expressing thyroid hormone receptors (TRs). T3 blocks the response to the oncogenic forms of the three ras isoforms (H-, K-, and N-ras) and both TR{alpha} and TR{beta} can mediate this action. The main target for induction of cyclin D1 transcription by oncogenic ras in neuroblastoma cells is a cyclic AMP response element (CRE) located in proximal promoter sequences, and T3 represses the transcriptional activity of b-Zip transcription factors such as CREB (CRE-binding protein) or ATF-2 (activation transcription factor 2) that are direct targets of Rsk2 and bind to this sequence. The hormone also blocks fibroblast transformation by oncogenic ras when TR is expressed. Furthermore, TRs act as suppressors of tumor formation by the oncogene in vivo in nude mice. The TR{beta} isoform has stronger antitransforming properties than the {alpha} isoform and can inhibit tumorigenesis even in hypothyroid mice. These results show the existence of a previously unrecognized transcriptional cross talk between the TRs and the ras oncogene which influences relevant processes such as cell proliferation, transformation, or tumorigenesis. 10.1128/MCB.24.17.7514-7523.2004 IS - 17 JF - Mol. Cell. Biol. EP - 7523 TI - The Thyroid Hormone Receptor Is a Suppressor of ras-Mediated Transcription, Proliferation, and Transformation VL - 24 SP - 7514 KW - hormone KW - nuclear KW - ras KW - receptor KW - regulation KW - thr KW - thyroid KW - transcription AU - Garcia-Silva, Susana AU - Aranda, Ana PY - 2004/09/01/ UR - http://dx.doi.org/10.1128/MCB.24.17.7514-7523.2004 ER -