Open AccessEnhancement of Cisplatin Sensitivity in High Mobility Group 2 cDNA‐transfected Human Lung Cancer Cells
Author(s) -
Arioka Hitoshi,
Nishio Kazuto,
Ishida Tomoyuki,
Fukumoto Hisaoh,
Fukuoka Kazuya,
Nomoto Taisuke,
Kurokawa Hirokazu,
Yokote Hideyuki,
Abe Shosaku,
Saijo Nagahiro
Publication year - 1999
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1999.tb00673.x
Subject(s) - cisplatin , transfection , microbiology and biotechnology , biology , cell culture , chemotherapy , genetics
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.