The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes

Francesca Carlomagno, Donata Vitagliano, Teresa Guida, Maria Napolitano, Giancarlo Vecchio, Alfredo Fusco, Aviv Gazit, Alexander Levitzki, Massimo Santoro

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Abstract

Oncogenic activation of the RET receptor tyrosine kinase is common in different human cancers. We found that the pyrazolo-pyrimidine PP1 inhibited RET-derived oncoproteins with a half maximal inhibitor concentration of 80 nM. Furthermore, RET/PTC3-transformed cells treated with 5 μM of PP1 lost proliferative autonomy and showed morphological reversion. PPI prevented the growth of two human papillary thyroid carcinoma cell lines that carry spontaneous RET/PTC1 rearrangements and blocked anchorage-independent growth and tumorigenicity in nude mice of NIH3T3 fibroblasts expressing the RET/PTC3 oncogene. These findings suggest targeting RET oncogenes with PP1 or related compounds as a novel treatment strategy for RET-associated neoplasms.

Original languageEnglish
Pages (from-to)1077-1082
Number of pages6
JournalCancer Research
Volume62
Issue number4
Publication statusPublished - 2002

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Carlomagno, F., Vitagliano, D., Guida, T., Napolitano, M., Vecchio, G., Fusco, A., Gazit, A., Levitzki, A., & Santoro, M. (2002). The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes. Cancer Research, 62(4), 1077-1082.