Rat Protein Tyrosine Phosphatase η Suppresses the Neoplastic Phenotype of Retrovirally Transformed Thyroid Cells through the Stabilization of p27^Kip1

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-Kioncogenes suppresses their malignant phenotype. Cell cycle analysis demonstrated that r-PTPη caused G₁ growth arrest and increased the cyclin-dependent kinase inhibitor p27^Kip1protein level by reducing the proteasome-dependent degradation rate. We propose that the r-PTPη tumor suppressor activity is mediated by p27^Kip1 protein stabilization, because suppression of p27^Kip1 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 p27^Kip1 protein level was regulated by the mitogen-activated protein (MAP) kinase pathway and that r-PTPη regulated p27^Kip1 stability by preventing v-mos- or v-ras-Ki-induced MAP kinase activation.

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Retraction for Trapasso et al., “Rat Protein Tyrosine Phosphatase η Suppresses the Neoplastic Phenotype of Retrovirally Transformed Thyroid Cells through the Stabilization of p27Kip1”

ACKNOWLEDGMENTS

This work was supported by grants from AIRC (Progetto Speciale Oncosoppressori), from the Progetto Finalizzato Biotecnologie of the CNR, the MURST projects Terapie antineoplastiche innovative and Piani di Potenziamento della Rete Scientifica e Tecnologica, and from the Ministero della Sanità. We thank the Associazione Partenopea per la Ricerche Oncologiche (APRO) for its support. Francesco Trapasso, Paola Bruni, Angelo Boccia, Gustavo Baldassarre, and Antonella Stella were recipients of a fellowship from the Fondazione Italiana per la Ricerca sul Cancro (FIRC).

We are grateful to Jean Gilder for editing the text.