Browse > Article
http://dx.doi.org/10.5808/GI.2008.6.1.036

Differential Expressions of Apoptosis-related Genes in Lung Cancer Cell Lines Determine the Responsiveness to Ionizing Radiation  

Lee, Su-Yeon (Seoul National University Bioinformatics)
Choi, Moon-Kyung (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
Lim, Jung-Min (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
Wu, Hong-Gyun (Department of Biochemistry, Radiation Oncology, Seoul National University College of Medicine)
Kim, Ju-Han (Seoul National University Bioinformatics)
Park, Woong-Yang (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
Abstract
Radiotherapy would be the choice of treatment for human cancers, because of high cost-effectiveness. However, a certain population of patients shows a resistance to radiotherapy and recurrence. In an effort to increase the efficacy of radiotherapy, many efforts were driven to find the genes causing the unresponsiveness to ionizing radiation. In this paper, we compared the gene expression profiles of two lung cancer cell lines, H460 and H1299, which showed differential responses to ionizing radiations. Each cell were irradiated at 2 Gy, and harvested after 0, 2, 4, 8, 12 and 24 hours to examine the expressions. Two-way ANOVA analysis on time-series experiments of two cells could select 2863 genes differentially expressed upon ionizing radiation among 32,321 genes in microarray (p<0.05). We classified these genes into 21 clusters by SOM clustering according to the interaction between cell types and time. Two SOM clusters were enriched with apoptosis-related genes in pathway analysis. One cluster contained higher levels of phosphatidyl inositol 3-phosphate kinase (PI3K) subunits in H1299, radio-resistant cells than H460, radiosensitive cells. TRAIL receptors were expressed in H460 cells while the decoy receptor for TRAIL was expressed in H1299 cells. From these results, we could characterize the differential responsiveness to ionizing radiation according to their differential expressions of apoptosis-related genes, which might be the candidates to increase the power of radiotherapy.
Keywords
apoptosis; ionizing radiation; lung cancer; radio-sensitivity; radiotherapy;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Pomeroy, S.L., Tamayo, P., Gaasenbeek, M., Sturla, L.M., Angelo, M., McLaughlin, M.E., Kim, J.Y., Goumnerova, L.C., Black, P.M., Lau, C., Allen, J.C., Zagzag, D., Olson, J.M., Curran, T., Wetmore, C., Biegel, J.A., Poggio, T., Mukherjee, S., Rifkin, R., Califano, A., Stolovitzky, G., Louis, D.N., Mesirov, J.P., Lander, E.S., and Golub, T.R. (2002). Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415, 436-442.   DOI   ScienceOn
2 Golub, T.R., Slonim, D.K., Tamayo, P., Huard, C., Gaasenbeek, M., Mesirov, J.P., Coller, H., Loh, M.L., Downing, J.R., Caligiuri, M.A., Bloomfield, C.D., and Lander, E.S. (1999). Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531-537.   DOI   ScienceOn
3 Klopp, A.H., and Eifel, P.J. (2006). Gene expression profiling in cervical cancer: state of the art and future directions. Cancer J. 12, 170-174.   DOI
4 Lee, M.S., Jun, D.H., Hwang, C.I., Park, S.S., Kang, J.J., Park, H.S., Kim, J., Kim, J.H., Seo, J.S., and Park, W.Y. (2006). Selection of neural differentiation-specific genes by comparing profiles of random differentiation. Stem Cells 24, 1946-1955.   DOI   ScienceOn
5 Park, W.Y., Hwang, C.I., Im, C.N., Kang, M.J., Woo, J.H., Kim, J.H., Kim, Y.S., Kim, H., Kim, K.A., Yu, H.J., Lee, S.J., Lee, Y.S., and Seo, J.S. (2002). Identification of radiation-specific responses from gene expression profile. Oncogene 21, 8521-8528.   DOI   ScienceOn
6 Tewari, D., Monk, B.J., Al-Ghazi, M.S., Parker, R., Heck, J.D., Burger, R.A., and Fruehauf, J.P. (2005). Gene expression profiling of in vitro radiation resistance in cervical carcinoma: a feasibility study. Gynecol. Oncol. 99, 84-91.   DOI   ScienceOn
7 Achary, M.P., Jaggernauth, W., Gross, E., Alfieri, A., Klinger, H.P., and Vikram, B. (2000). Cell lines from the same cervical carcinoma but with different radiosensitivities exhibit different cDNA microarray patterns of gene expression. Cytogenet Cell Genet. 91, 39-43.   DOI   ScienceOn
8 Kim, I.J., Lim, S.B., Kang, H.C., Chang, H.J., Ahn, S.A., Park, H.W., Jang, S.G., Park, J.H., Kim, D.Y., Jung, K.H., Choi, H.S., Jeong, S.Y., Sohn, D.K., Kim, D.W., and Park, J.G. (2007). Microarray gene expression profiling for predicting complete response to preoperative chemoradiotherapy in patients with advanced rectal cancer. Dis. Colon. Rectum. 50, 1342-1353.   DOI
9 Fukuda, K., Sakakura, C., Miyagawa, K., Kuriu, Y., Kin, S., Nakase, Y., Hagiwara, A., Mitsufuji, S., Okazaki, Y., Hayashizaki, Y., and Yamagishi, H. (2004). Differential gene expression profiles of radioresistant oesophageal cancer cell lines established by continuous fractionated irradiation. Br. J. Cancer 91, 1543-1550.   DOI   ScienceOn
10 Dennis, G.Jr., Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Lane, H.C., and Lempicki, R.A. (2003). DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 4, P3.   DOI
11 Lossos, I.S., Czerwinski, D.K., Alizadeh, A.A., Wechser, M.A., Tibshirani, R., Botstein, D., and Levy, R. (2004). Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N. Engl. J. Med. 350, 1828-1837.   DOI   ScienceOn
12 Wong, Y.F., Sahota, D.S., Cheung, T.H., Lo, K.W., Yim, S.F., Chung, T.K., Chang, A.M., and Smith, D.I. (2006). Gene expression pattern associated with radiotherapy sensitivity in cervical cancer. Cancer J. 12, 189-193.   DOI
13 Nishizaki, M., Meyn, R.E., Levy, L.B., Atkinson, E.N., White, R.A., Roth, J.A., and Ji, L. (2001). Synergistic inhibition of human lung cancer cell growth by adenovirus-mediated wild-type p53 gene transfer in combination with docetaxel and radiation therapeutics in vitro and in vivo. Clin. Cancer Res. 7, 2887-2897.
14 Weidhaas, J.B., Babar, I., Nallur, S.M., Trang, P., Roush, S., Boehm, M., Gillespie, E., and Slack, F.J. (2007). MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res. 67, 11111-11116.   DOI   ScienceOn
15 Snyder, A.R., and Morgan, W.F. (2004). Gene expression profiling after irradiation: clues to understanding acute and persistent responses? Cancer Metastasis Rev. 23, 259-268.   DOI   ScienceOn
16 Wu, H.G., Bang, Y.J., Choi, E.K., Ahn, Y.C., Kim, Y.W., Lim, T.H., Suh, C., Park, K., and Park, C.I. (2002). Phase I study of weekly docetaxel and cisplatin concurrent with thoracic radiotherapy in Stage III non-small-cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 52, 75-80.   DOI   ScienceOn