Distinct roles of the ERK pathway in modulating apoptosis of Ras-transformed and non-transformed cells induced by anticancer agent FR901228.
Ectopic expression of oncogenic H-Ras in cells results in increases of cell susceptibility to the anticancer agent FR901228. Investigating the roles of Ras-induced pathways in FR901228-induced apoptosis, we have found that the phosphatidylinositol 3-kinase pathway plays an anti-apoptotic role, whereas the stress-activated protein kinase p38 pathway plays a pro-apoptotic role in FR901228-induced apoptosis. Interestingly, the extracellular signal-regulated kinase (ERK) pathway plays an anti-apoptotic role in non-transformed cells; however, it plays a pro-apoptotic role in Ras-transformed cells in response to FR901228 treatment. An essential role of the ERK pathway in regulating caspase-3 contents may contribute to its pro-apoptotic role in Ras-transformed cells.
Song
Ping
P
Anticancer Molecular Oncology Laboratory, Department of Pathobiology College of Veterinary Medicine, The University of Tennessee Knoxville, TN 37996, USA.
Wei
Jinxiong
J
Wang
Hwa-Chain Robert
HC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002461:Cell Line, Transformed; D047630:Depsipeptides / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; C087123:romidepsin; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D015689:Oncogene Protein p21(ras)