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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1999 Jan;90(1):108–115. doi: 10.1111/j.1349-7006.1999.tb00673.x

Enhancement of Cisplatin Sensitivity in High Mobility Group 2 cDNA‐transfected Human Lung Cancer Cells

Hitoshi Arioka 1,2, Kazuto Nishio 1,✉, Tomoyuki Ishida 1, Hisaoh Fukumoto 1, Kazuya Fukuoka 1, Taisuke Nomoto 1, Hirokazu Kurokawa 1, Hideyuki Yokote 1, Shosaku Abe 2, Nagahiro Saijo 1
PMCID: PMC5925981  PMID: 10076573

Abstract

To elucidate the role of high mobility group 2 protein (HMG2) in cis‐diamminedichloroplatinum (II) (cisplatin, CDDP) sensitivity, we constructed a human HMG2‐transfected human non‐small cell lung cancer cell line, PC‐14/HMG2. The HMG2 mRNA expression level was approximately twice those of parental PC‐14 and mock‐transfected PC‐14/CMV. Gel mobility shift assay revealed a CDDP‐treated DNA‐protein complex in the nuclear extract of PC‐14/HMG2, which was not found in the extracts of PC‐14 and PC‐14/CMV. This complex formation was subject to competition by CDDP‐treated non‐specific salmon sperm DNA, indicating that ectopic HMG2 recognizes CDDP‐damaged DNA. PC‐14/HMG2 showed more than 3‐fold higher sensitivity to CDDP than PC‐14 and PC‐14/CMV. The intracellular platinum content of PC‐14/HMG2 after exposure to 300 μM CDDP was 1.1 and 1.5 times that of PC‐14 and PC‐14/CMV, respectively. Cellular glutathione levels were not different in these cell lines. Repair of DNA interstrand cross‐links determined by alkaline elution assay was decreased in PC‐14/HMG2. These results suggest that HMG2 may enhance the CDDP sensitivity of cells by inhibiting repair of the DNA lesion induced by CDDP.

Keywords: HMG2, Cisplatin, Interstrand cross‐link‐DNA repair

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