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 Transwell invasion assay. Activities of signal molecules in epidermal growth factor receptor-mitogen-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.
Han
Fei
F
Department of Pathology, Fudan University, Shanghai, China.
Gu
Donghua
D
Chen
Qi
Q
Zhu
Hongguang
H
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051242:Caveolin 1; D034741:RNA, Small Interfering; D066246:ErbB Receptors; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases