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Mol Cancer. 2008 Jan 11;7:5. doi: 10.1186/1476-4598-7-5.

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

Author information

  • 1Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, USA. fxc155@psu.edu

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSION:

These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human pancreatic cancer is a p21 CKI pathway, expanding strategies for diagnosis and treatment of these neoplasias.

PMID:
18190706
[PubMed - indexed for MEDLINE]
PMCID:
PMC2253554
Free PMC Article

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