| Co-Investigator(Kenkyū-buntansha) |
SEKI Naohiko CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, Associate Professor, 大学院・医学研究院, 助教授 (50345013)
SHIMADA Hideaki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 大学院・医学研究院, 講師 (20292691)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
To identify genes associated with radioresistance (RR) of cancer and to establish a useful method of predicting radiotherapeutic effectiveness, we examined gene expression patterns in 6 oral carcinoma derived cell lines and 12 esophageal carcinoma derived cell lines that exhibited different responses to ionizing radiation (IR) by clonogenic survival assay using in-house cDNA microarray consisting of 2,201 human genes, oligo-array, AceGene^<TM> (Hitachi Soft-ware Engineering), consisting 30,000 probes, and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR). These analyses showed overexpression of 7 genes in the radioresistant cell lines, and 20 genes in the radiosensitive cell lines. The expression changes in 14 of these 27 genes, such as Cytokeratin 18,DTNBP1,ASNA1,Tcp20,Cyclophilin F,KIAA0218,HBp17, and so on, were confirmed with QRT-PCR. Of these, Tcp20 whose expression were remarkably elevated in radioresistant HSC2 cells after IR was investigated. Dose escalation of X-rays resulted in an enhanced Tcp20 expression level in HSC2 cells as compared to radiosensitive HSC3 cells (P<0.05, Mann-Whitney's U-test). These results suggest that the identified genes including Tcp20 may play an important role in conferring RR to OSCC. Gene function analysis by transformation with over-expression vector and siRNA of these genes revealed that suppression of Ku80 gene expression induces more radio sensitivity.
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