Differential Gene Expression Profiles of Radioresistant Non–Small-Cell Lung Cancer Cell Lines Established by Fractionated Irradiation: Tumor Protein p53-Inducible Protein 3 Confers Sensitivity to Ionizing Radiation

• Published in: International journal of radiation oncology, biology, physics Vol. 77; no. 3; pp. 858 - 866
• Main Authors: Lee, Young Sook, Ph.D, Oh, Jung-Hwa, M.S, Yoon, Seokjoo, Ph.D, Kwon, Myung-Sang, Ph.D, Song, Chang-Woo, Ph.D, Kim, Ki-Hwan, Ph.D, Cho, Moon-June, M.D., Ph.D, Mollah, Mohamad Lalmodin, M.S, Je, Young Jin, B.S, Kim, Yoon-Dong, M.D., Ph.D, Kim, Chang Deok, Ph.D, Lee, Jeung-Hoon, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2010; Elsevier
• Subjects: Biological and medical sciences; BODY; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - radiotherapy; cDNA microarray; Cell Line, Tumor; DISEASES; FRACTIONATED IRRADIATION; Gene Expression Profiling; GENES; Genetic Markers; Hematology, Oncology and Palliative Medicine; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; IRRADIATION; Lung Neoplasms - genetics; Lung Neoplasms - radiotherapy; LUNGS; Medical sciences; MEDICINE; NEOPLASMS; Non–small-cell lung cancer; NUCLEAR MEDICINE; or PIG3; ORGANIC COMPOUNDS; ORGANS; Pneumology; PROTEINS; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Radiation Tolerance - genetics; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; Radioresistance; RADIOSENSITIVITY; RADIOTHERAPY; RESPIRATORY SYSTEM; SENSITIVITY; THERAPY; Tumor protein p53-inducible protein 3 (TP53I3; Tumors of the respiratory system and mediastinum; Non–small-cell lung cancer; Radioresistance; cDNA microarray; or PIG3; Tumor protein p53-inducible protein 3 (TP53I3; Lung disease; Respiratory disease; p53 Protein; Tumor protein p53-inducible protein 3 (TP53I3, or PIG3); Non-small-cell lung cancer; Malignant tumor; non-small cell lung carcinoma; Gene expression; Ionizing radiation; Sensitivity; Cell line; Irradiation; Bronchus disease; eDNA microarray; Cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2009.12.076

Purpose Despite the widespread use of radiotherapy as a local and regional modality for the treatment of cancer, some non–small-cell lung cancers commonly develop resistance to radiation. We thus sought to clarify the molecular mechanisms underlying resistance to radiation. Methods and Materials We established the radioresistant cell line H460R from radiosensitive parental H460 cells. To identify the radioresistance-related genes, we performed microarray analysis and selected several candidate genes. Results Clonogenic and MTT assays showed that H460R was 10-fold more resistant to radiation than H460. Microarray analysis indicated that the expression levels of 1,463 genes were altered more than 1.5-fold in H460R compared with parental H460. To evaluate the putative functional role, we selected one interesting gene tumor protein p53-inducible protein 3 (TP53I3), because that this gene was significantly downregulated in radioresistant H460R cells and that it was predicted to link p53-dependent cell death signaling. Interestingly, messenger ribonucleic acid expression of TP53I3 differed in X-ray–irradiated H460 and H460R cells, and overexpression of TP53I3 significantly affected the cellular radiosensitivity of H460R cells. Conclusions These results show that H460R may be useful in searching for candidate genes that are responsible for radioresistance and elucidating the molecular mechanism of radioresistance.