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The roles of phosphotyrosines-294, -404, and -451 in RET/PTC1-induced thyroid tumor formation

Oncogene volume 21, pages 8166–8172 (2002)Cite this article

Abstract

RET/PTC1 is a rearranged form of the RET proto-oncogene detected in human papillary thyroid carcinomas. We previously showed that thyroid-targeted expression of RET/PTC1 leads to thyroid tumor formation in Tg-PTC1 transgenic mice. Signal transduction pathways mediated by phosphotyrosine 294, 404, or 451 in RET/PTC1 have been shown to be critical for RET-induced transforming activity in vitro. To investigate the contribution of these signaling pathways in RET/PTC1-induced thyroid tumor formation in vivo, we generated and characterized transgenic mice expressing thyroid-targeted RET/PTC1 mutants carrying a site-directed mutation changing tyrosine (Y) to phenylalanine (F) at the residue 294, 404, or 451. In contrast to the 100% tumor formation rate in Tg-PTC1 transgenic mice, tumor formation rates were significantly decreased in Tg-PTC1-Y294F (6%), Tg-PTC1-Y404F (41%), and Tg-PTC1-Y451F (30%) transgenic mice. This indicates that signaling pathways mediated by pY294, pY404, and pY451 do play a role in RET/PTC1-induced tumor formation. However, as tumors are still able to form in some mice within these three mutant transgenic groups, it indicates that none of the signaling pathways mediated by pY294, pY404, or pY451, are solely essential for RET/PTC1-induced tumor formation.

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Acknowledgements

This work was supported in part by National Institutes of Health Grant RO1 CA60074 (to SM Jhiang).

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Authors and Affiliations

  1. Department of Physiology and Cell Biology, The Ohio State University, Columbus, 43210, Ohio, OH, USA

    Tara LF Buckwalter, Anjli Venkateswaran, Marc Lavender, Krista MD La Perle, Je-Yoel Cho & Sissy M Jhiang

  2. Department of Veterinary Biosciences, The Ohio State University, Columbus, 43210, Ohio, OH, USA

    Krista MD La Perle

  3. Department of Pediatrics, The Ohio State University, Columbus, 43210, Ohio, OH, USA

    Michael L Robinson

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  1. Tara LF Buckwalter
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  2. Anjli Venkateswaran
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  5. Je-Yoel Cho
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Correspondence to Sissy M Jhiang.

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Buckwalter, T., Venkateswaran, A., Lavender, M. et al. The roles of phosphotyrosines-294, -404, and -451 in RET/PTC1-induced thyroid tumor formation. Oncogene 21, 8166–8172 (2002). https://doi.org/10.1038/sj.onc.1205938

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