Restoration of receptor-type protein tyrosine phosphatase {eta} function inhibits human pancreatic carcinoma cell growth in vitro and in vivo

DEP-1/HPTPeta, 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. Inaddition, loss of DEP-1/HPTPeta heterozygosity has been described in mammary,lung and colon primary tumors. We now show that DEP-1/HPTPeta is drasticallyreduced in several cell lines originating from human epithelial pancreaticcarcinomas compared with normal pancreatic tissue. We also show that the infection of AsPC1 and PSN1 cells with a recombinant adenovirus carrying r-PTPeta cDNA (the rat homolog of DEP-1/HPTPeta) inhibits their proliferation. Flow cytometric analysis of the infected cells demonstrated that restoration of r-PTPeta activity disrupts their cell cycle and leads to apoptosis. Finally, the growth of PSN1 xenograft tumors was blocked by the intratumoral injection of arecombinant adeno-associated virus carrying r-PTPeta. The data suggest that restoration of DEP-1/HPTPeta expression could be a useful tool for the gene therapy of human pancreatic cancers.