Lipocalin-2 is associated with radioresistance in oral cancer and lung cancer cells

Shiiba,Masashi; Saito,Kengo; Fushimi,Kazuaki; Ishigami,Takashi; Shinozuka,Keiji; Nakashima,Dai; Kouzu,Yukinao; Koike,Hirofumi; Kasamatsu,Atsushi; Sakamoto,Yosuke; Ogawara,Katsunori; Uzawa,Katsuhiro; Takiguchi,Yuichi; Tanzawa,Hideki

doi:10.3892/ijo.2013.1815

Lipocalin-2 is associated with radioresistance in oral cancer and lung cancer cells

Authors:
- Masashi Shiiba
- Kengo Saito
- Kazuaki Fushimi
- Takashi Ishigami
- Keiji Shinozuka
- Dai Nakashima
- Yukinao Kouzu
- Hirofumi Koike
- Atsushi Kasamatsu
- Yosuke Sakamoto
- Katsunori Ogawara
- Katsuhiro Uzawa
- Yuichi Takiguchi
- Hideki Tanzawa
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Affiliations: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan, Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan, Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
Published online on: February 8, 2013 https://doi.org/10.3892/ijo.2013.1815
Pages: 1197-1204

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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.

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