PTEN/pAkt/p53 signaling pathway correlates with the radioresponse of non-small cell lung cancer.
The sensitivity or resistance of cancer cells and normal tissues to ionizing radiation plays an important role in the clinical setting of lung cancer treatment. However, to date the exact molecular mechanisms of intrinsic radiosensitivity have not been well explained. In this study, we compared the radiosensitivity or radioresistance in two non-small cell lung cancers (NSCLCs), H460 and A549, and investigated the signaling pathways that confer radioresistance. H460 cells showed a significant G(2)/M arrest after 12 h of irradiation (5 Gy), reaching 60% of G(2)/M phase arrest. A549 cells also showed a significant G(2)/M arrest after 12 h of exposure; however, this arrest completely disappeared after 24 h of exposure. A549 has higher methylated CpG sites in PTEN, which is correlated with tumor radioresistance in some cancer cells, than H460 cells, and the average of the extent of the methylation was approximately 4.3 times higher in A549 cells than in H460 cells. As a result, PTEN expression was lower in A549 than in H460. Conducting Western blot analysis, we found that PTEN acted as a negative regulator for pAkt, and the pAkt acted as a negative regulator for p53 expression. According to the above results, we concluded that the radiosensitivity shown in H460 cells may be due to the higher expression of PTEN through p53 signaling pathway.
Jung
Il Lae
IL
Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Yuseong, Daejeon 305-600, Korea.
Kang
Hyo Jin
HJ
Kim
Kug Chan
KC
Kim
In Gyu
IG
D001483:Base Sequence; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy; D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy; D008938:Mitosis / Q000528:radiation effects; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011836:Radiation Tolerance / Q000528:radiation effects; D011839:Radiation, Ionizing; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000528:radiation effects; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human