• 作者： Ben-Kuen Chen, Tein-Yi Tsai, Huei-Sheng Huang, Lei-Chin Chen, Wei-Chiao Chang, Song-Bor Tsai, Wen-Chang Chang
• 作者服務機構： Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
• 中文摘要： --
• 英文摘要： The functional role of mitogen-activated protein kinase(MAPK) signaling and c-Jun induction in phorbol12-myristate 13-acetate (PMA)-induced human 12(S)-lipoxy-genase gene expression was studied in human epider-moid carcinoma A431 cells. Among the family of MAPK,PMA only increased the activity of extracellular signal-reg-ulated kinase (ERK). Treatment of cells with PD98059,which is an inhibitor of mitogen-activated protein kinaseki nase (MEK), decreased the PMA-induced expression of12 (S)-lipoxygenase. Transfection of cells with Ras, Rafand ERK2 dominant negative mutants inhibited the PMA-induced promoter activation of the 12(S)-lipoxygenasegene in all cases. PMA-induced expression of c-Jun wasinhibited by pretreatment with PD98059. Following treat-ment with PMA, the interaction between c-Jun and simianvirus 40 promoter factor 1 (Sp1) in cells increased withtime. Enhancement of binding between the c-Jun-Sp1complex and the Sp1 oligonucleotide was observed incells treated with PMA, suggesting the possible interac-tion of c-Jun-Sp1 with GC-rich binding sites in the genepromoter. These results indicate that PMA treatment in-duced ERK activation mainly through the Raf-MEK-ERKsignaling pathway following induction of c-Jun expres-sion, and the formation of the c-Jun-Sp1 complex. Finally,PMA activated the promoter activity of the 12(S)-lipoxy-genase gene in cells overexpressing protein kinase C(PKC) but not PKC , indicating that PKC played the func-tional role in mediating the gene activation of 12(S)-lip-oxygenase induced by PMA.
• 中文關鍵字： --
• 英文關鍵字： Phorbol 12-myristate 13-acetate, Extracellular signal-regulated kinase, c-Jun, Sp1, 12(S)- Lipoxygenase