Identification of candidate radioresistant genes in human squamous cell carcinoma cells through gene expression analysis using DNA microarrays.
Radiation therapy is currently the standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Individual OSCCs display a wide range of radiosensitivity (RS). To identify genes associated with radioresistance (RR) of OSCC and establish a useful method of predicting radio-therapeutic effectiveness, we examined the gene expression patterns of OSCC cell lines that exhibited different responses to ionizing radiation (IR) by clonogenic survival assay using an in-house cDNA microarray consisting of 2,201 human genes and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR). Microarray analysis showed overexpression of 7 genes in the radioresistant cell line, HSC2, and 2 genes in the radiosensitive cell line, HSC3. The changes in expression levels in 7 of 9 genes (Cytokeratin18, DTNBP1, ASNA1, Tcp20, Cyclophilin F, KIAA0218, and HBp17) were confirmed with QRT-PCR. Of these, the genetic alterations of Tcp20, whose expression was remarkably elevated in radioresistant HSC2 cells after IR, were investigated. The escalation of X-ray doses resulted in an enhanced Tcp20 expression level in HSC2 cells compared to radiosensitive HSC3 cells (P<0.05, Mann-Whitney U test). These results suggest that the identified genes, which include Tcp20, may play an important role in conferring RR to OSCC, and could also be useful in identifying cases of OSCC with more radioresistance.
Higo
Morihiro
M
Department of Clinical Molecular Biology, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Uzawa
Katsuhiro
K
Kouzu
Yukinao
Y
Bukawa
Hiroki
H
Nimura
Yoshinori
Y
Seki
Naohiko
N
Tanzawa
Hideki
H
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D002470:Cell Survival; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000473:pathology
D056404:Chaperonin Containing TCP-1; D018833:Chaperonins