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insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth

World Journal of Gastroenterology 2009年第27期15卷 3355-3366页

作者： Sarah K Johnson Randy S Haun Department of Pathology Winthrop P. Rockefeller Cancer Institute University of Arkansas for Medical SciencesLittle Rock Arkansas AR 72205 United States

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 and phosphatidylinositol activated protein kinase 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.

关键词： insulin-like growth factor-binding protein 5 Extracellular signal-regulated mitogen activated protein kinases Cyclin-dependent kinase inhibitor p27 Pancreatic neoplasms

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