Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Cordes, N; Frickz, S; Brunner, TB; Pilarsky, C; Grutzmann, R; Siposs, B; Kloppels, G; McKenna, WG; Bernhard, EJ.
Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1
ONCOGENE. 2007; 26(48): 6851-6862.
Doi: 10.1038/sj.onc.1210498
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Brunner Thomas Baptist
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- Abstract:
- 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 beta 1-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 Panel cell lines. The cell lines showed significant radio-sensitization after knockdown of Cav-1, beta 1-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 3 beta, 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 beta 1-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.
- Find related publications in this database (Keywords)
- caveolin-1
- ionizing radiation
- beta 1-integrin
- FAK
- pancreatic cancer