Genes and molecular pathways related to radioresistance of oral squamous cell carcinoma cells.
To identify genes associated with radioresistant oral squamous cell carcinoma (OSCC), we compared gene expression signatures between OSCC cell lines exhibiting radioresistance and cells with radiosensitivity after X-ray irradiation in a dose-dependent manner using Affymetrix GeneChip analysis with Human Genome-U133 plus 2.0 GeneChip. The microarray data identified 167 genes that were significantly overexpressed in radioresistant cells after X-ray irradiation. Among the genes identified, 40 were mapped to 3 highly significant genetic networks identified by the Ingenuity Pathway Analysis tool. Gene ontology analysis showed that cancer-related function had the highest significance. The 40 genes included 25 cancer-related genes that formed 1 network and were categorized by function into growth and proliferation, apoptosis, and adhesion. Furthermore, real-time quantitative reverse transcriptase-polymerase chain reaction showed that the mRNA expression levels of the 25 genes were higher in radioresistant cells than in radiosensitive cells in a dose-dependent manner and in a time-dependent manner. Our results suggest that the identified genes help to elucidate the molecular mechanisms of the radioresistance of OSCC and could be radiotherapeutic molecular markers for choosing the appropriate radiotherapy for this disease.
Ishigami
Takashi
T
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8607, Japan.
Uzawa
Katsuhiro
K
Higo
Morihiro
M
Nomura
Hitomi
H
Saito
Kengo
K
Kato
Yoshikuni
Y
Nakashima
Dai
D
Shiiba
Masashi
M
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Kawata
Tetsuya
T
Ito
Hisao
H
Tanzawa
Hideki
H
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003199:Computer Systems; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011836:Radiation Tolerance / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods