Enhanced Effect of Connexin 43 on Cisplatin-Induced Cytotoxicity in Mesothelioma Cells
スポンサーリンク
概要
- 論文の詳細を見る
The expression levels of connexin (Cx) proteins, which are gap junction (GJ) components, are often decreased in many cancers, and restoring their levels has been shown to have antitumor effects. Previously, dysfunctional gap junctional intercellular communication (GJIC) has been observed in several malignant mesotheliomas (MMs), and among the many Cx proteins, Cx43 is prominently expressed in nontumorigenic mesothelial tissues. Therefore, we investigated whether Cx43 upregulation has an antitumor effect on an MM cell line (H28 cell), especially with regard to drug resistance. After treatment with the chemotherapeutic agent cisplatin (CDDP), MM cell viability significantly decreased, and apoptosis induction was observed in Cx43-transfected clones. A specific GJIC inhibitor could not abrogate this effect. On the other hand, the Src protein is known to phosphorylate Cx43, which results in GJIC inhibition. This suggests that Src activity might also be regulated by the hyperexpression of Cx43. In fact, the Src protein level was decreased in Cx43-transfected clones. Moreover, Src inhibition reinforced CDDP cytotoxicity in parental H28 cells. These data suggest that Cx43 could improve the resistance to CDDP in a GJIC-independent manner, which may be partly mediated by the suppression of Src activity.
- 2009-08-20
著者
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UENO Koichi
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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Yamaura Katsunori
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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Sato Hiromi
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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NAGASHIMA Yoji
Department of Pathology, Graduate School of Medicine, Yokohama City University
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Ueno K
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Yamada Ryota
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Nagashima Yoji
Department Of Molecular Tumor Pathology Yokohama City University School Of Medicine
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Nagashima Yoji
Department Of Molecular Pathology Graduate School Of Medicine Yokohama City University
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Sato Hiromi
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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IWATA Hiroki
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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TAKANO Yasuyuki
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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OKUZAWA Hiroko
Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, C
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YANO Tomohiro
Project for Complementary Factors, National Institute of Health and Nutrition
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Ueno K
Laboratory Of Biochemical Pharmacology And Biotoxicology Faculty Of Pharmaceutical Sciences Chiba Un
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Ueno Koichi
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Ueno Koichi
Laboratory Of Biochemical Pharmacology And Biotoxicology Department Of Drug Evaluation And Toxicolog
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Ueno Koichi
Departments Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Ch
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Iwata Hiroki
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Yano Tomohiro
Project For Complementary Factors National Institute Of Health And Nutrition
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Yano Tomohiro
Division Of Applied Food National Institute Of Health And Nutrition
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Okuzawa Hiroko
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Ueno Koichi
Department Of Drug Evaluation And Toxicological Sciences Faculty Of Pharmaceutical Sciences Chiba Un
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Ueno K
Kinki Univ. Nara Jpn
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Ueno Koichi
Dep. Of Geriatric Pharmacology Graduate School Of Pharmaceutical Sciences Chiba Univ.
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Yamaura Katsunori
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Yamaura Katsunori
Department Of Geriatric Pharmacology & Therapeutics Graduate School Of Pharmaceutical Sciences C
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Takano Yasuyuki
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Ueno Koichi
Department Of Geriatric Pharmacology And Therapeutics Graduate School Of Pharmaceutical Sciences Chi
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Yano Tomohiro
Department Of Life Environmental Sciences Faculty Of Life Sciences Toyo University
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Sato Hiromi
Department of Applied Chemistry, Graduate School of Engineering, Tohoku University, 6-6-11-1302 Aoba, Aramaki, Aoba-ku, Sendai 980-8579, Japan
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UENO Koichi
Department of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University
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