Rat protein tyrosine phosphatase η suppresses the neoplastic phenotype of retrovirally transformed thyroid cells through the stabilization of p27Kip1

F. Trapasso, R. Iuliano, A. Boccia, A. Stella, R. Visconti, P. Bruni, G. Baldassarre, M. Santoro, G. Viglietto, A. Fusco

Research output: Contribution to journalArticlepeer-review

Abstract

The r-PTPη gene encodes a rat receptor-type protein tyrosine phosphatase whose expression is negatively regulated by neoplastic cell transformation. Here we first demonstrate a dramatic reduction in DEP-1/HPTPη (the human homolog of r-PTPη) expression in a panel of human thyroid carcinomas. Subsequently, we show that the reexpression of the r-PTPη gene in highly malignant rat thyroid cells transformed by retroviruses carrying the v-mos and v-ras-Ki oncogenes suppresses their malignant phenotype. Cell cycle analysis demonstrated that r-PTPη caused G1 growth arrest and increased the cyclin-dependent kinase inhibitor p27Kip1 protein level by reducing the proteasome-dependent degradation rate. We propose that the r-PTPη tumor suppressor activity is mediated by p27Kip1 protein stabilization, because suppression of p27Kip1 protein synthesis using p27-specific antisense oligonucleotides blocked the growth-inhibitory effect induced by r-PTPη. Furthermore, we provide evidence that in v-mos- or v-ras-Ki-transformed thyroid cells, the p27Kip1 protein level was regulated by the mitogen-activated protein (MAP) kinase pathway and that r-PTPη regulated p27Kip1 stability by preventing v-mos- or v-ras-Ki-induced MAP kinase activation.

Original languageEnglish
Pages (from-to)9236-9246
Number of pages11
JournalMolecular and Cellular Biology
Volume20
Issue number24
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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