Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1

Oncogene. 2007 Oct 18;26(48):6851-62. doi: 10.1038/sj.onc.1210498. Epub 2007 Apr 30.


Caveolin-1 (Cav-1) is an integral transmembrane protein and a critical component in interactions of integrin receptors with cytoskeleton-associated and signaling molecules. Since integrin-mediated cell adhesion generates signals conferring radiation resistance, we examined the effects of small interfering RNA-mediated knockdown of Cav-1 alone or in combination with beta1-integrin or focal adhesion kinase (FAK) on radiation survival and proliferation of pancreatic carcinoma cell lines. Irradiation induced Cav-1 expression in PATU8902, MiaPaCa2 and Panc1 cell lines. The cell lines showed significant radiosensitization after knockdown of Cav-1, beta1-integrin or FAK and cholesterol depletion by beta-cyclodextrin relative to nonspecific controls. Under knockdown conditions, proliferation of non-irradiated and irradiated cells was significantly attenuated relative to controls. These findings correlated with changes in expression or phosphorylation of Akt, glycogen synthase kinase 3beta, Paxillin, Src, c-Jun N-terminal kinase and mitogen-activated protein kinase. Analysis of DNA microarray data revealed a Cav-1 overexpression in a subset of pancreatic ductal adenocarcinoma samples. The data presented show, for the first time, that disruption of interactions of Cav-1 with beta1-integrin or FAK affects radiation survival and proliferation of pancreatic carcinoma cells and suggest that Cav-1 is critical to these processes. These results indicate that strategies targeting Cav-1 may be useful as an approach to improve conventional therapies, including radiotherapy, for pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Caveolin 1 / metabolism*
  • Cell Adhesion
  • Cell Cycle / physiology
  • Cell Cycle / radiation effects
  • Cell Proliferation / radiation effects
  • Colony-Forming Units Assay
  • Fluorescent Antibody Technique
  • Focal Adhesion Kinase 1 / antagonists & inhibitors
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Gene Expression Profiling
  • Humans
  • Integrin beta1 / chemistry
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / radiotherapy*
  • Paxillin / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • RNA, Small Interfering / pharmacology
  • Radiation Tolerance / physiology*
  • Signal Transduction
  • X-Rays


  • Caveolin 1
  • Integrin beta1
  • Paxillin
  • RNA, Small Interfering
  • Phosphatidylinositol 3-Kinases
  • Focal Adhesion Kinase 1
  • Proto-Oncogene Proteins pp60(c-src)
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases