title: Lipocalin-2 is associated with radioresistance in oral cancer and lung cancer cells.
abstract: The aim of the present study was to identify a target molecule that could predict the efficacy of radiotherapy in oral squamous cell carcinoma (OSCC). We used DNA microarray analysis to identify differences in gene expression after X-ray irradiation. We compared the gene expression profiles between X-ray (8 Gy)-irradiated Ca9-22 cells (an OSCC-derived cell line) and unirradiated Ca9-22 cells. A total of 167 genes with a 2-fold higher level of expression induced by X-ray irradiation were identified. Lipocalin-2 (LCN2) had the greatest increase in expression after X-ray irradiation, and it was categorized in a network that has cancer-related functions with the Ingenuity Pathway Analysis tool. Upregulated expression of LCN2 mRNA was validated by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. When the LCN2 gene was knocked down in OSCC cells (Ca9-22 and HSC-2) and lung cancer cells (A549) by using small interfering RNA, the radiosensitivity of these cells was enhanced. Our findings suggest that the overexpression of LCN2 is likely associated with radioresistance in oral cancer and lung cancer cells, and that LCN2 expression levels could be used to predict radioresistance. Thus, regulating the expression or function of LCN2 could enhance the radiation response, resulting in a favorable outcome of radiotherapy.
authors: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan. m.shiiba@faculty.chiba-u.jp
authors: Masashi
authors: M
authors: Shiiba
authors: Kengo
authors: K
authors: Saito
authors: Kazuaki
authors: K
authors: Fushimi
authors: Takashi
authors: T
authors: Ishigami
authors: Keiji
authors: K
authors: Shinozuka
authors: Dai
authors: D
authors: Nakashima
authors: Yukinao
authors: Y
authors: Kouzu
authors: Hirofumi
authors: H
authors: Koike
authors: Atsushi
authors: A
authors: Kasamatsu
authors: Yosuke
authors: Y
authors: Sakamoto
authors: Katsunori
authors: K
authors: Ogawara
authors: Katsuhiro
authors: K
authors: Uzawa
authors: Yuichi
authors: Y
authors: Takiguchi
authors: Hideki
authors: H
authors: Tanzawa
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms; D009062:Mouth Neoplasms; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D059467:Transcriptome / Q000528:radiation effects
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins