Carcinogenesis Advance Access published online on July 1, 2004
Carcinogenesis, doi:10.1093/carcin/bgh224
© 2004 by Oxford University Press
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1 Kimmel Cancer Institute, Thomas Jefferson University, 233S 10th Street, Philadelphia, PA 19107, USA; Dipartimento di Medicina Sperimentale e Clinica, Università "Magna Græcia", via T. Campanella, 5, I-88100 Catanzaro, Italy
* To whom correspondence should be addressed. E-mail: afusco{at}napoli.com.
DEP-1/HPTP
Revised June 14, 2004
Accepted June 22, 2004
CANCER BIOLOGY
Restoration of receptor-type protein tyrosine phosphatase
function inhibits human pancreatic carcinoma cell growth in vitro and in vivo
2 Kimmel Cancer Institute, Thomas Jefferson University, 233S 10th Street, Philadelphia, PA 19107, USA
3 Dipartimento di Medicina Sperimentale e Clinica, Università "Magna Græcia", via T. Campanella, 5, I-88100 Catanzaro, Italy
4 Department of Neurosurgery, CNS Gene Therapy Center, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA
5 Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli "Federico II", via Pansini, 5, I-80131 Naples, Italy
Abstract 
, 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 to normal pancreatic tissue. We also show that the infection of AsPC1 and PSN1 cells with a recombinant adenovirus carrying r-PTP cDNA (the rat homologue 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 adenoassociated virus carrying r-PTP. These data suggest that restoration of DEP-1/HPTP expression could be a useful tool for the gene therapy of human pancreatic cancers.; pancreas; transformation; gene therapy.
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