Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jul 21, 2009; 15(27): 3355-3366
Published online Jul 21, 2009. doi: 10.3748/wjg.15.3355
Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth
Sarah K Johnson, Randy S Haun
Sarah K Johnson, Randy S Haun, Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, AR 72205, United States
Author contributions: Johnson SK designed and performed the experiments; Haun RS supervised the project; Johnson SK and Haun RS wrote the paper.
Correspondence to: Randy S Haun, PhD, Associate Professor, Department of Pathology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Slot 753, Little Rock, Arkansas, AR 72205, United States. haunrandys@uams.edu
Telephone: +1-501-6868594
Fax: +1-501-6866517
Received: March 12, 2009
Revised: June 3, 2009
Accepted: June 10, 2009
Published online: July 21, 2009
Abstract

AIM: To investigate the functional significance of insulin-like growth factor binding protein-5 (IGFBP-5) overexpression in pancreatic cancer (PaC).

METHODS: The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses. Changes in cell survival and signal transduction were evaluated after mitogen activated protein kinase and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.

RESULTS: After serum deprivation, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival.

CONCLUSION: These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth.

Keywords: Insulin-like growth factor-binding protein 5; Extracellular signal-regulated mitogen activated protein kinases; Cyclin-dependent kinase inhibitor p27; Pancreatic neoplasms