Activation of JNK by TPA promotes apoptosis via PKC pathway in gastric cancer cells

作者: Yan Chen

DOI: 10.3748/WJG.V8.I6.1014

关键词:

摘要: AIM: JNK cascade plays an important role in cell proliferation, differentiation and apoptosis. However, the exact function of for apoptosis induction remains largely unknown. In this study, activation stimulated by TPA process its signaling transduction pathway gastric cancer cells were investigated determined. METHODS: Expressions mRNA protein detected Northern blot Western blot. Transcription activity was measured transient transfection CAT assay. Apoptotic displayed through staining nucleus with DAPI observed under fluorescence microscope. The apoptotic index determined counting 1000 randomly. RESULTS: rapidly TPA, reached highest peak within 3 hr, then decreased a time-dependent manner, but expression level induced always keeping higher than that untreated cells. Similar pattern seen c-jun TPA. significantly activated transcriptional activator protein-1 TPA-dosedependent manner. Furthermore, mediated PKC pathway. Treatment specific inhibitor, Wortmannin, led to repression even presence More importantly, all these effects associated inducted obviously became smaller rounded, their nuclei condensation fragmentation brightly stained chromatin. suppression resulted decrease dramatically from 32.56 % 8.71 %.

参考文章(47)
H. Mischak, J.A. Goodnight, W. Kolch, G. Martiny-Baron, C. Schaechtle, M.G. Kazanietz, P.M. Blumberg, J.H. Pierce, J.F. Mushinski, Overexpression of protein kinase C-delta and -epsilon in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity. Journal of Biological Chemistry. ,vol. 268, pp. 6090- 6096 ,(1993) , 10.1016/S0021-9258(18)53223-3
H. van Dam, D. Wilhelm, I. Herr, A. Steffen, P. Herrlich, P. Angel, ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents. The EMBO Journal. ,vol. 14, pp. 1798- 1811 ,(1995) , 10.1002/J.1460-2075.1995.TB07168.X
F. Fleischer, Stress kinase inhibition modulates acute experimental pancreatitis World Journal of Gastroenterology. ,vol. 7, pp. 259- 265 ,(2001) , 10.3748/WJG.V7.I2.259
Elisabetta Rovida, Fabio Marra, Manuela Baccarini, Persio Dello Sbarba, Constitutive activation of the MAPK pathway mediates v-fes-induced mitogenesis in murine macrophages. Blood. ,vol. 95, pp. 3959- 3963 ,(2000) , 10.1182/BLOOD.V95.12.3959
Zerihun Assefa, Annelies Vantieghem, Wim Declercq, Peter Vandenabeele, Jackie R. Vandenheede, Wilfried Merlevede, Peter de Witte, Patrizia Agostinis, The Activation of the c-Jun N-terminal Kinase and p38 Mitogen-activated Protein Kinase Signaling Pathways Protects HeLa Cells from Apoptosis Following Photodynamic Therapy with Hypericin Journal of Biological Chemistry. ,vol. 274, pp. 8788- 8796 ,(1999) , 10.1074/JBC.274.13.8788
Marcel Verheij, Ron Bose, Xin Hua Lin, Bei Yao, W. David Jarvis, Steven Grant, Michael J. Birrer, Eva Szabo, Leonard I. Zon, John M. Kyriakis, Adriana Haimovitz-Friedman, Zvi Fuks, Richard N. Kolesnick, Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature. ,vol. 380, pp. 75- 79 ,(1996) , 10.1038/380075A0
Michael J. Cross, Allison Stewart, Matthew N. Hodgkin, David J. Kerr, Michael J.O. Wakelam, Wortmannin and Its Structural Analogue Demethoxyviridin Inhibit Stimulated Phospholipase A2 Activity in Swiss 3T3 Cells: WORTMANNIN IS NOT A SPECIFIC INHIBITOR OF PHOSPHATIDYLINOSITOL 3-KINASE Journal of Biological Chemistry. ,vol. 270, pp. 25352- 25355 ,(1995) , 10.1074/JBC.270.43.25352