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. In addition, loss of DEP-1/HPTPeta heterozygosity has been described in mammary, lung and colon primary tumors. We now show that DEP-1/HPTPeta 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-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 a recombinant 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.
Trapasso
Francesco
F
Kimmel Cancer Institute, Thomas Jefferson University, 233S 10th Street, Philadelphia, PA 19107, USA.
Yendamuri
Sai
S
Dumon
Kristoffel R
KR
Iuliano
Rodolfo
R
Cesari
Rossano
R
Feig
Byron
B
Seto
Robin
R
Infante
Luisa
L
Ishii
Hideshi
H
Vecchione
Andrea
A
During
Matthew J
MJ
Croce
Carlo M
CM
Fusco
Alfredo
A
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D007700:Kinetics; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3