title: Pro-apoptotic role of integrin β3 in glioma cells.
abstract: Malignant gliomas are the most destructive type of brain cancer. In order to gain a better understanding of the molecular mechanisms of glioma cell death and survival, we previously established an alkylating agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-resistant variant of C6 rat glioma cells. Proteomic analysis indicated a significant down-regulation of integrin beta 3 (ITGB3) in the BCNU-resistant C6R cells. Re-expression of ITGB3 in C6R cells restored the BCNU sensitivity. In U87MG, U373MG, and T98G human glioma cells, there was a positive correlation between ITGB3 expression and the sensitivity to BCNU and etoposide, suggesting an important role of ITGB3 in glioma cell death. Over-expression of ITGB3 cDNA significantly increased the sensitivity of the human glioma cells to the anticancer drug-induced apoptosis. Nitric oxide showed an additive effect on the anticancer drug-induced glioma cell death by increasing ITGB3 expression. Subsequent dissection of signaling pathways indicated that extracellular signal-regulated kinase and unligated integrin-mediated cell death pathway may be involved in the pro-apoptotic role of ITGB3 in glioma cells. These results implicate ITGB3 in glioma cell death/survival and drug resistance.
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Long Tai
authors.initials: LT
authors.lastname: Zheng
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002330:Carmustine / Q000494:pharmacology; D045744:Cell Line, Tumor; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013223:Statistics as Topic; D013778:Tetrazolium Salts; D013844:Thiazoles; D019096:Vitronectin / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D039661:Integrin beta3; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D019096:Vitronectin; D009569:Nitric Oxide; D005047:Etoposide; C022616:thiazolyl blue; D002330:Carmustine