BACKGROUND AND PURPOSE: High levels of hypoxia inducible factor (HIF)-1α in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1α on radioresistance under normoxia, the sensitivity towards irradiation was measured in human tumor cell lines that differ significantly in their basal HIF-1α levels. MATERIAL AND METHODS: HIF-1α levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1α, HIF-2α, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1α siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. RESULTS: According to their basal HIF-1α status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1α expressors. The functionality of the high basal HIF-1α expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1α. Linear regression analysis revealed no correlation between basal HIF-1α levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. CONCLUSION: Our data suggest that basal HIF-1α levels in human tumor cell lines do not predict their radiosensitivity under normoxia.
BACKGROUND AND PURPOSE: High levels of hypoxia inducible factor (HIF)-1α in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1α on radioresistance under normoxia, the sensitivity towards irradiation was measured in humantumor cell lines that differ significantly in their basal HIF-1α levels. MATERIAL AND METHODS: HIF-1α levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1α, HIF-2α, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1α siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. RESULTS: According to their basal HIF-1α status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1α expressors. The functionality of the high basal HIF-1α expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1α. Linear regression analysis revealed no correlation between basal HIF-1α levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. CONCLUSION: Our data suggest that basal HIF-1α levels in humantumor cell lines do not predict their radiosensitivity under normoxia.
Authors: Daniel Zips; Simon Böke; Theresa Kroeber; Andreas Meinzer; Kerstin Brüchner; Howard D Thames; Michael Baumann; Ala Yaromina Journal: Strahlenther Onkol Date: 2011-04-26 Impact factor: 3.621
Authors: Duyen T Dang; Fang Chen; Lawrence B Gardner; Jordan M Cummins; Carlo Rago; Fred Bunz; Sergey V Kantsevoy; Long H Dang Journal: Cancer Res Date: 2006-02-01 Impact factor: 12.701
Authors: Olga Aprelikova; Silvia Pandolfi; Sean Tackett; Mark Ferreira; Konstantin Salnikow; Yvona Ward; John I Risinger; J Carl Barrett; John Niederhuber Journal: Cancer Res Date: 2009-01-15 Impact factor: 12.701
Authors: L Helbig; A Yaromina; S N Sriramareddy; S Böke; L Koi; H D Thames; M Baumann; D Zips Journal: Strahlenther Onkol Date: 2012-09-29 Impact factor: 3.621
Authors: P C Lara; M Lloret; A Valenciano; B Clavo; B Pinar; A Rey; L A Henríquez-Hernández Journal: Strahlenther Onkol Date: 2012-11-01 Impact factor: 3.621