An adenovirus carrying the rat protein tyrosine phosphatase η suppresses the growth of human thyroid carcinoma cell lines in vitro and in vivo

We demonstrated previously that rat tyrosine phosphatase r-PTPη expression was suppressed in rat and human thyroid neoplastic cells, and that restoration of r-PTPη expression reverted the malignant phenotype. To investigate the potential of this gene for cancer therapy, we generated an adenovirus carrying the r-PTPη cDNA (Ad-r-PTPη). This virus infected human thyroid carcinoma cells and overexpressed the r-PTPη protein. Overexpression of r-PTPη significantly inhibited the growth of four thyroid carcinoma cell lines. Cell growth inhibition was associated with down-regulation of extracellular signal-regulated kinase 1/2 activity, with increased levels of the cell-cycle inhibitor p27kip1 protein and with dephosphorylation of PLCγ1, a substrate of DEP-1, the human homologue of r-PTPη. Finally, the growth of xenograft tumors induced in athymic mice by anaplastic thyroid carcinoma ARO cells transduced with the Ad-r-PTPη virus was drastically reduced. These data suggest that gene therapy based on restoration of PTPη function has potential in the treatment of human thyroid malignant neoplasias.