Susceptible genes and molecular pathways related to heavy ion irradiation in oral squamous cell carcinoma cells.
OBJECTIVE
Heavy ion beams are high linear energy transfer (LET) radiation characterized by a higher relative biologic effectiveness than low LET radiation. The aim of the current study was to determine the difference of gene expression between heavy ion beams and X-rays in oral squamous cell carcinoma (OSCC)-derived cells.


METHODS
The OSCC cells were irradiated with accelerated carbon or neon ion irradiation or X-rays using three different doses. We sought to identify genes the expression of which is affected by carbon and neon ion irradiation using Affymetrix GeneChip analysis. The identified genes were analyzed using the Ingenuity Pathway Analysis Tool to investigate the functional network and gene ontology. Changes in mRNA expression in the genes were assessed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).


RESULTS
The microarray analysis identified 84 genes that were modulated by carbon and neon ion irradiation at all doses in OSCC cells. Among the genes, three genes (TGFBR2, SMURF2, and BMP7) and two genes (CCND1 and E2F3), respectively, were found to be involved in the transforming growth factor beta-signaling pathway and cell cycle:G1/S checkpoint regulation pathway. The qRT-PCR data from the five genes after heavy ion irradiation were consistent with the microarray data (P < 0.01).


CONCLUSIONS
Our findings should serve as a basis for global characterization of radiation-regulated genes and pathways in heavy ion-irradiated OSCC.
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kazuaki
K
Fushimi
Katsuhiro
K
Uzawa
Takashi
T
Ishigami
Nobuharu
N
Yamamoto
Tetsuya
T
Kawata
Takahiko
T
Shibahara
Hisao
H
Ito
Jun-Etsu
JE
Mizoe
Hirohiko
H
Tsujii
Hideki
H
Tanzawa
D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D002244:Carbon; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D019938:Cyclin D1 / Q000235:genetics; D050699:E2F3 Transcription Factor / Q000235:genetics; D015870:Gene Expression; D020450:Heavy Ions; D006801:Humans; D018499:Linear Energy Transfer / Q000235:genetics; D046228:Microarray Analysis; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D009356:Neon; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; C530104:CCND1 protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D019938:Cyclin D1; D009356:Neon; D002244:Carbon; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II