The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer

Molecular Cancer
Fan ChengIan S Zagon

Abstract

Pancreatic cancer is the 4th leading cause of death from cancer in the U.S. The opioid growth factor (OGF; [Met5]-enkephalin) and the OGF receptor form an inhibitory growth regulatory system involved in the pathogenesis and treatment of pancreatic cancer. The OGF-OGFr axis influences the G0/G1 phase of the cell cycle. In this investigation, we elucidate the pathway of OGF in the cell cycle. Using BxPC-3 cells, OGF decreased phosphorylation of retinoblastoma (Rb) protein without changing total Rb. This change was correlated with reduced cyclin-dependent kinase protein (Cdk) 2 kinase activity, but not total Cdk2. OGF treatment increased cyclin-dependent kinase inhibitor (CKI) p21 protein expression in comparison to controls, as well levels of p21 complexed with Cdk2. Naloxone abolished the increased expression of p21 protein by OGF, suggesting a receptor-mediated activity. p21 specific siRNAs blocked OGF's repressive action on proliferation in BxPC-3, PANC-1, and Capan-2 cells; cells transfected with negative control siRNA had no alteration in p21 expression, and therefore were inhibited by OGF. These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human pancreatic cancer is a p21 CK...Continue Reading

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Citations

Jul 2, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Fan ChengIan S Zagon
Nov 20, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Diego M AvellaKevin F Staveley-O'Carroll
Mar 5, 2010·Molecular Medicine·Daniela SpanoAchille Iolascon
Mar 8, 2014·World Journal of Gastroenterology : WJG·Ian S Zagon, Patricia J McLaughlin
Oct 2, 2009·Peptides·Richard J Bodnar
Mar 2, 2016·International Immunopharmacology·Dingliang ZhaoFengping Shan
Sep 7, 2014·Archivum Immunologiae Et Therapiae Experimentalis·Magdalena Mizerska-Dudka, Martyna Kandefer-Szerszeń
Jul 17, 2013·Experimental Biology and Medicine·Ian S ZagonPatricia J McLaughlin
May 16, 2008·Experimental Biology and Medicine·Ian S ZagonPatricia J McLaughlin
Mar 9, 2018·International Journal of Cancer. Journal International Du Cancer·Dirk Theile, Gerd Mikus
Jul 17, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Fan ChengIan S Zagon
Mar 2, 2012·Expert Review of Gastroenterology & Hepatology·Ian S Zagon, Patricia J McLaughlin
Feb 18, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Patricia J McLaughlinIan S Zagon
Aug 7, 2013·Experimental Biology and Medicine·Ian S ZagonPatricia J McLaughlin
Mar 20, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Renee N DonahueIan S Zagon
Aug 14, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ian S ZagonPatricia J McLaughlin
Oct 27, 2010·Experimental Biology and Medicine·Patricia J McLaughlinIan S Zagon
Jul 24, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shih Sheng JiangI-Shou Chang
Jun 15, 2020·European Journal of Pharmacology·Yali TuoMing Xiang
Aug 25, 2021·International Immunopharmacology·Hai HuangFengping Shan

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Methods Mentioned

BETA
xenografts
confocal microscopy
flow cytometry
immunoprecipitation
protein assay

Software Mentioned

QuickOne
Modfit

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