Restoration of receptor-type protein tyrosine phosphatase ? function inhibits human pancreatic carcinoma cell growth in vitro and in vivo.

DEP-1/HPTP?, a receptor-type protein tyrosine phosphatase, is a candidate tumor suppressor gene because its expression was blocked in rat and human thyroid transformed cells, and its restoration reverted their neoplastic phenotype. In addition, loss of DEP-1/HPTP? heterozygosity has been described in mammary, lung and colon primary tumors. We now show that DEP-1/HPTP? is drastically reduced in several cell lines originating from human epithelial pancreatic carcinomas compared with normal pancreatic tissue. We also show that the infection of AsPC1 and PSN1 cells with a recombinant adenovirus carrying r-PTP? cDNA (the rat homolog of DEP-1/HPTP?) inhibits their proliferation. Flow cytometric analysis of the infected cells demonstrated that restoration of r-PTP? activity disrupts their cell cycle and leads to apoptosis. Finally, the growth of PSN1 xenograft tumors was blocked by the intratumoral injection of a recombinant adeno-associated virus carrying r-PTP?. The data suggest that restoration of DEP-1/HPTP? expression could be a useful tool for the gene therapy of human pancreatic cancers. [ABSTRACT FROM AUTHOR]