Prevention and delay in progression of human pancreatic cancer by stable overexpression of the opioid growth factor receptor.
This study examined overexpression of the opioid growth factor receptor (OGFr) in pancreatic cancer cells and phenotypic changes in tumorigenicity. Tumors of MIA PaCa-2 cells transfected with OGFr cDNA (OGFr-1) had 3.3 times more OGFr than empty vector (EV) neoplasias, and 4.3 times more OGFr than tumors from wild-type (WT) mice. No differences in OGFr binding were detected between tumors of EV and WT animals. Tumor incidence in OGFr-1 animals was reduced by up to 50% from EV mice. Latency times for OGFr-1 tumor expression were increased 30%, tumor volume was decreased 70%, and DNA synthesis was reduced 24% relative to EV mice. Exogenous OGF reduced OGFr-1 tumor volume up to 55% compared to OGFr-1 mice given vehicle. These data support OGFr gene function as a regulator of cell proliferation that impacts on tumorigenic expression, and suggest that molecular and pharmacological manipulation of OGFr may prevent or delay human pancreatic cancer.
Zagon
Ian S
IS
Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. isz1@psu.edu
Kreiner
Shawn
S
Heslop
Jeffery J
JJ
Conway
Andrea B
AB
Morgan
Clinton R
CR
McLaughlin
Patricia J
PJ
D000818:Animals; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000502:physiology; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor