Identification of the product of two oncogenic rearranged forms of the RET proto-oncogene in papillary thyroid carcinomas

C. Lanzi, M. G. Borrello, I. Bongarzone, A. Migliazza, A. Fusco, M. Grieco, M. Santoro, R. A. Gambetta, F. Zunino, G. Della Porta, M. A. Pierotti

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Abstract

In papillary thyroid carcinomas, we have identified two tumor-specific rearrangements of the RET proto-oncogene leading to the formation of different transforming fusion products sharing the tyrosine kinase (tk) domain of the proto-oncogene and designated ptc-1 and ptc-2. We have analysed ptc-l and ptc-2 products by immunoprecipitation with specific anti-RET antibodies followed by immunoblotting with the same reagent or with antibodies specific for phosphotyrosine (P-tyr) residues. The anti-RET antibodies were reactive with 64-kDa (p64ptc-1) and 81-kDa (p81ptc-2) proteins from lysates of ptc-1 and ptc-2 transformed cells, respectively, and identified two proteins of 140 kDa and 160 kDa from extracts of SK-N-SH, a neuroblastoma cell line previously shown to express two differently glycosylated forms of the normal RE T product. The anti P-tyr antibodies, while detecting the same p64ptc-1 and p81ptc-2 proteins from ptc-1 and ptc-2 extracts, did not show any specific band in the neuroblastoma lysates. An additional set of experiments led us to conclude that, whereas the normal product of the RET proto-oncogene is a membrane-associated receptor-like molecule not intrinsically phosphorylated on tyrosine, both oncogenic forms of RET, ptc-1 and ptc-2, are constitutively phosphorylated on tyrosine, display an 'in vitro' autophosphorylation activity, are translocated from the membrane to the cytoplasm and are apparently unaffected by protein kinase C modulation.

Original languageEnglish
Pages (from-to)2189-2194
Number of pages6
JournalOncogene
Volume7
Issue number11
Publication statusPublished - Nov 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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