[Expressions of stem cell factor and hypoxia inducible factor 1 alpha in pancreatic cancer cells and related mechanism].

ABSTRACT

Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 µmol/L). Real-time fluorescent quantitative PCR (qRT-PCR) was performed to detect the level of HIF-1α mRNA, and Western blotting to detect the HIF-1α protein level, the phosphorylation levels of ERK1/2 and AKT. Results SCF and HIF-1α were up-regulated in pancreatic cancer samples and they had an obvious positive correlation. In PANC-1 cells, SCF didn't affect the expression of HIF-1α mRNA, but up-regulated the expression of HIF-1α protein in a dose-dependent manner. Gleevec inhibited the SCF-induced up-regulation of HIF-1α protein, but did not affect the mRNA. And Gleevec blocked the phosphorylation of AKT and ERK1/2. Conclusion SCF/c-KIT can up-regulate the protein expression of HIF-1α by activating AKT and ERK signaling pathways in pancreatic cancer cells.