Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15

Joseph Tung Chieh Chang, Shih Hsuan Chan, Chien Yu Lin, Ting Yang Lin, Hung Ming Wang, Chun Ta Liao, Tzu Hao Wang, Li Yu Lee, Ann Joy Cheng*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

85 Scopus citations

Abstract

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 G2-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.

Original languageEnglish
Pages (from-to)2271-2279
Number of pages9
JournalMolecular Cancer Therapeutics
Volume6
Issue number8
DOIs
StatePublished - 01 08 2007

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