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

查看全文 作　　者：Sarah K [1]Johnson;Randy S [1]Haun

机构地区：[1]Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences,Little Rock, Arkansas, AR 72205, United States

出　　处：《World Journal of Gastroenterology》索引2009年第15卷第27期,共12页

基　　金：Supported by A grant from the Arkansas Master Tobacco Settlement and Arkansas Biosciences Institute 摘　　要：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. 关键词：胰岛素样生长因子结合蛋白细胞生长胰腺癌磷脂酰肌醇3激酶细胞外信号调节激酶 DNA合成免疫印迹分析细胞数量

相关文献

参考文献（35）
引证文献（5）
耦合文献（0）

参考文献(35)

引证文献(5)

互联网出版许可证新出网证(渝)字10号全国400电话 - 免长途话费

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

参考文献(35)

引证文献(5)

用户提示