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The steroid receptor coactivator-3 is a tumor promoter in a mouse model of thyroid cancer

Oncogene volume 27, pages 823–830 (2008)Cite this article

Abstract

The molecular genetic events underlying thyroid carcinogenesis are not well understood. Mice harboring a dominant-negative mutant thyroid hormone receptor-β (TRβPV/PV mice) spontaneously develop follicular thyroid carcinoma similar to human cancer. The present study aimed to elucidate the role of the steroid receptor coactivator-3 (SRC-3) in thyroid carcinogenesis in vivo by using the offspring from the cross of TRβPV/PV and SRC-3−/− mice. TRβPV/PV mice deficient in SRC-3 (TRβPV/PVSRC-3−/− mice) had significantly increased survival, decreased thyroid tumor growth, delayed tumor progression and lower incidence of distant metastasis as compared with TRβPV/PV mice with SRC-3 (TRβPV/PVSRC-3+/+ mice). Further, in vivo and in vitro analyses of multiple signaling pathways indicated that SRC-3 deficiency could lead to (1) inhibition of cell cycle progression at the G1/S transition via controlling the expression of cell cycle regulators, such as E2F1; (2) induction of apoptosis by controlling the expression of the Bcl-2 and caspase-3 genes and (3) suppression of neovascularization and metastasis, at least in part, through modulating the vascular endothelial growth factor gene expression. Taken together, SRC-3 could play important roles through regulating multiple target genes and signaling pathways during thyroid carcinogenesis, understanding of which should direct future therapeutic options for thyroid cancer.

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Acknowledgements

We thank B O’Malley for SRC-3 null mice and R Wu for the anti-SRC-3 antibodies. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    H Ying & S-Y Cheng

  2. Department of Pathology, Wake Forest University, Winston-Salem, NC, USA

    M C Willingham

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  1. H Ying
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  2. M C Willingham
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  3. S-Y Cheng
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Correspondence to S-Y Cheng.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Ying, H., Willingham, M. & Cheng, SY. The steroid receptor coactivator-3 is a tumor promoter in a mouse model of thyroid cancer. Oncogene 27, 823–830 (2008). https://doi.org/10.1038/sj.onc.1210680

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