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

Arioka, Hitoshi; Nishio, Kazuto; Ishida, Tomoyuki; Fukumoto, Hisao; Fukuoka, Kazuya; Nomoto, Tomoko; Kurokawa, Hirokazu; Yokote, Hideyuki; Abe, Shosaku; Saijo, Nagahiro

doi:10.1111/j.1349-7006.1999.tb00673.x

Cited by 25 publications

(25 citation statements)

References 30 publications

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“…Consistent with this notion, hormone-induced HMGB1 up-regulation in MCF-7 breast cancer cells correlates with enhanced cisplatin sensitivity (27). Increased cisplatin sensitivity was also observed in a lung adenocarcinoma cell line transfected with a plasmid expressing HMGB2, a protein with more than 80% identity to HMGB1 (28). A recent study, however, showed that loss of NHP6A, an abundant HMG box protein in Saccharomyces cerevisiae, sensitized yeast to cisplatin, suggesting that a mechanism other than repair shielding was in effect in the yeast system (29).…”

supporting

confidence: 63%

Cisplatin Sensitivity in Hmgb1−/− and Hmgb1+/+ Mouse Cells

Wei¹,

Burenkova

Lippard

2003

Journal of Biological Chemistry

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The study presented here investigates the effect of HMGB1 knockout on the sensitivity of mouse embryonic fibroblasts treated with the anticancer drug cisplatin. We evaluated both the growth inhibition by cisplatin and cisplatin-induced cell death in the Hmgb1 ؊/؊ cells and its wild-type counterpart. No significant differences were observed in the responses of these cells to cisplatin, indicating that HMGB1 does not play a significant role in modulating the cellular responses to cisplatin in this context. Since HMGB1 significantly enhances the cytotoxicity of cisplatin in other cells, these results illustrate the importance of cell type in determining the ability of this and probably other cisplatin-DNA-binding proteins to influence the efficacy of the drug.cis-Diamminedichloroplatinum(II) (cisplatin) 1 is one of the most widely used anticancer drugs for the treatment of a variety of human malignancies (1). Whereas cisplatin is extremely effective in treating testicular cancer, the cure rate being Ͼ90% when tumors are promptly diagnosed (2), the curative potential of the drug against other tumors, such as ovarian, breast, and lung cancers, is significantly undermined by intrinsic and acquired resistance (3). Determining the factors that influence cellular sensitivity to cisplatin is thus important for understanding the anticancer activity of cisplatin and for developing a more effective platinum-based chemotherapy.The cytotoxicity of cisplatin arises from its ability to react with DNA and form covalent DNA adducts (4). The major adducts, 1,2-intrastrand d(GpG) and d(ApG) platinum-DNA cross-links, are formed by coordination of the {Pt(NH 3 ) 2 } 2ϩ moiety to the N 7 atoms of adjacent purines in double-stranded DNA. The cisplatin modification produces distinct changes in the architecture of the DNA duplex that inhibit replication and transcription and stimulate nucleotide excision repair (1). Cisplatin damage throughout the genome leads to cell cycle arrest and apoptosis (5). Moreover, cisplatin-DNA adducts are recognized by a variety of cellular proteins, a process that may affect the fate of platinum-DNA lesions and the responsiveness of tumor cells to cisplatin treatment (6, 7). Recognition of cisplatin-modified DNA by damage recognition proteins in the nucleotide excision repair pathway leads to the removal of platinum lesions and restoration of genomic integrity. Studies have suggested that increase in the repair of platinum-DNA adducts is key to cisplatin resistance (3). Several proteins not involved in repair, including HMGB1, TATA-binding protein, and other structure-specific recognition proteins, also bind tightly to the major platinum-DNA adducts (1). The role that these proteins might play in mediating the cytotoxicity of cisplatin is a subject of much current interest. One hypothesis, which has been proposed in various studies, suggests that the binding of these proteins to platinum-DNA adducts blocks the removal of DNA lesions, thereby enhancing the sensitivity of cells to cisplatin (8 -14). This model...

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supporting

confidence: 63%

Cisplatin Sensitivity in Hmgb1−/− and Hmgb1+/+ Mouse Cells

Wei¹,

Burenkova

Lippard

2003

Journal of Biological Chemistry

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“…Depleting HMG1 and HMG2 from cell extracts by immunoprecipitation enhanced excision repair of cisplatin-modified DNA (22). Furthermore, introducing HMG2 by transfection enhanced the cisplatin sensitivity of a lung adenocarcinoma cell line (23). Until the present work, however, there was, to our knowledge, no evidence that overexpression of an HMG domain protein via a natural signal transduction pathway in human cancer cells could increase their sensitivity to cisplatin.…”

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confidence: 53%

Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin

Liang²,

Lippard³

2000

Proc. Natl. Acad. Sci. U.S.A.

192

156

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Cisplatin is an anticancer drug that has enjoyed remarkable success against testicular tumors, but dose limiting side-effects have limited its application against a broader range of cancers. Previous studies have shown that high-mobility group (HMG) domain proteins such as HMG1 sensitize cells to cisplatin by shielding its major DNA adducts from nucleotide excision repair. Estrogen treatment increases HMG1 mRNA levels in breast cancer MCF-7 cells. Herein, we describe that treatment of human cancer cells having steroid hormone receptors with the appropriate hormone, estrogen and͞or progesterone, significantly increases the potency of cisplatin and its analogue carboplatin by causing the overexpression of HMG1. These findings suggest that the proper combination of these drugs, which are already approved by the Food and Drug Administration, could have potential benefit in treating tumors such as ovarian or breast that carry the hormone receptors.

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“…These results indicate that HMGB2 may exert a role as an antiapoptotic oncoprotein in HCC. On the other hand, the introduction of HMGB2 gene into human lung cancer cells increased cisplatin sensitivity (26), indicating that the role of HMGB2 might be dependent on types of cancer. HMGB2 suppressed the transcriptional activity of p53 in osteosarcoma (27), whereas HMGB2 enhanced the transcriptional activity of p53 in E6-positive cervical cancer, HeLa (22).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of High-Mobility Group Box 2 Is Associated with Tumor Aggressiveness and Prognosis of Hepatocellular Carcinoma

Kwon

Kim

Park

et al. 2010

Clinical Cancer Research

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Purpose: We investigated the expression of high-mobility group box 2 (HMGB2) in patients with hepatocellular carcinoma (HCC) and its clinical effects with underlying mechanisms.Experimental Design: HMGB2 mRNA levels were measured in 334 HCC patients by real-time reverse transcription-PCR and HMGB2 protein levels in 173 HCC patients by immunohistochemical studies. The HMGB2 expression level was measured by Western blotting for three HCC cell lines. To clarify the precise role of HMGB2 on cell proliferation, we did in vitro analysis with expression vectors and small interfering RNAs.Results: HMGB2 mRNA and protein expression were significantly higher in HCC than in noncancerous surrounding tissues (P < 0.0001) and showed a positive correlation (ρ = 0.35, P < 0.001). HMGB2 overexpression was significantly correlated with shorter overall survival time, both at mRNA (P = 0.0054) and protein level (P = 0.023). Moreover, HMGB2 mRNA level was an independent prognostic factor for overall survival in a multivariate analysis (P = 0.0037). HMGB2 knockdown by small interfering RNAs decreased cell proliferation, and overexpression of HMGB2 by expression vectors diminished cisplatinand etoposide-induced cell death.Conclusions: Our clinical and in vitro data suggest that HMGB2 plays a significant role in tumor development and prognosis of HCC. These results can partly be explained by altered cell proliferations by HMGB2 associated with the antiapoptotic pathway. Clin Cancer Res; 16(22); 5511-21. ©2010 AACR.

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

Cited by 25 publications

References 30 publications

Cisplatin Sensitivity in Hmgb1−/− and Hmgb1+/+ Mouse Cells

Cisplatin Sensitivity in Hmgb1−/− and Hmgb1+/+ Mouse Cells

Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin

Overexpression of High-Mobility Group Box 2 Is Associated with Tumor Aggressiveness and Prognosis of Hepatocellular Carcinoma

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