Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15.
Radiotherapy is the major treatment modality for nasopharyngeal cancer (NPC), but in some cases, the disease is radioresistant. We designed this study to identify genes that may be involved in this resistance. We first established two radioresistant subclone cell lines derived from NPC parental cell lines (NPC-076 and NPC-BM1) by treating the cells with four rounds of sublethal ionizing radiation. cDNA microarray analysis was then done, comparing the two resistant cell lines with their corresponding parental cell lines. Seven genes were found to be up-regulated in radioresistant subclones, including gp96 and GDF15, which had shown highest overexpressions. We constructed small interfering RNA plasmids (gp96si and GDF15si) and transfected them into NPC cells to knock down these genes and examine whether this changed their response to radiation. Both gp96si and GDF15si transfectants had radiation-induced growth delay and reduction in colonogenic survival compared with control cells. Knockdown of either gp96 or GDF15 increased the proportion of the cells in G(2)-M phase, the most radiosensitive phase of the cell cycle. We have therefore identified at least two genes, gp96 and GDF15, involved in radioresistance of NPC cell lines and showed that knockdown of the genes enhances radiosensitivity.
Chang
Joseph Tung-Chieh
JT
Department of Radiation Oncology, Chang Gung University, 259 Wen-Hwa 1st Road, Taoyuan 333, Taiwan.
Chan
Shih-Hsuan
SH
Lin
Chien-Yu
CY
Lin
Ting-Yang
TY
Wang
Hung-Ming
HM
Liao
Chun-Ta
CT
Wang
Tzu-Hao
TH
Lee
Li-Yu
LY
Cheng
Ann-Joy
AJ
D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival; D002999:Clone Cells; D016195:G2 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm; D005822:Genetic Vectors; D008562:Membrane Glycoproteins / Q000235:genetics*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D014162:Transfection; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics
D019485:Bone Morphogenetic Proteins; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C053387:endoplasmin