Caveolin-1 Acts as a Tumor Suppressor by Down-Regulating Epidermal Growth Factor Receptor-Mitogen-Activated Protein Kinase Signaling Pathway in Pancreatic Carcinoma Cell Lines

Objective: To investigate the effect of caveolin-1 (cav1) in pancreatic carcinoma panc1 cell growth in vitro and in vivo. Methods: Caveolin-1 gene was transferred into panc1 cells, and stably overexpressed cav1 clones were established. Proliferation and anchorage-independent growth capacity in vitro were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and colony formation assays in soft agar. Flow cytometry was used to analyze cell cycle and apoptosis. The invasion ability was measured by Trans-well invasion assay. Activities of signal molecules in epidermal growth factor receptorYmitogen-activated protein kinase (EGFR-MAPK) signal pathway were determined by Western blots. Tumor growth in vivo was evaluated by tumorigenesis assay in nude mice. Results: Stably overexpressing cav1 cells exhibited slower growth and reduced the capacity of anchorage-independent growth. Overexpression of cav1 reduced cell invasion capacity and promoted cell apoptosis. The activities of EGFR-MAPK signal pathway were also inhibited significantly by overexpression of cav1, in addition, overexpression of cav1 in panc1 cells reduced tumor formation in vivo. Conclusions: The cav1 may act as a candidate tumor suppressor gene in human panceatic carcinoma, and this effect may be related with the inhibition of EGFR-MAPK signal cascade.