TY - JOUR
T1 - Basal HIF-1α expression levels are not predictive for radiosensitivity of human cancer cell lines
AU - Schilling, D.
AU - Bayer, C.
AU - Emmerich, K.
AU - Molls, M.
AU - Vaupel, P.
AU - Huber, R. M.
AU - Multhoff, G.
N1 - Funding Information:
The authors would like to thank Ines Nachtigall for her excellent technical assistance. This work was supported by the Helmholtz Zentrum München (Clinical cooperation group: Innate Immunity in Tumor Biology), the Deutsche Forschungsgemeinschaft (SFB 824/1; Cluster of Excellence 158: Munich-Centre of Advanced Photonics, INST. 95/980-1 FUGG, Gulmay irradiation device), BMBF (MOBITUM, 01EZ0826; Kompetenzverbund Strahlenforschung, 03NUK007E; Leading-Edge Cluster m4– Personalized Medicine and Targeted Therapies, 01EX1021 C), and the European Union (EU-CARDIORISK, FP7-211403).
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Basal HIF-1α expression
KW - Carbonic anhydrase IX
KW - Normoxia
KW - Radiosensitivity
UR - http://www.scopus.com/inward/record.url?scp=84862667418&partnerID=8YFLogxK
U2 - 10.1007/s00066-011-0051-6
DO - 10.1007/s00066-011-0051-6
M3 - Article
C2 - 22318330
AN - SCOPUS:84862667418
SN - 0179-7158
VL - 188
SP - 353
EP - 358
JO - Strahlentherapie und Onkologie
JF - Strahlentherapie und Onkologie
IS - 4
ER -