title: Selection for TRAIL resistance results in melanoma cells with high proliferative potential.
abstract: To better understand the outcome of the interaction between TNF-related apoptosis-inducing factor (TRAIL) and tumor cells, we studied TRAIL-resistant melanoma cells resulting from prolonged exposure to TRAIL and found that they had higher proliferative activity than the parental cells both in vitro and in vivo. This was associated with reduced p53 and p21 expression and increased activation of Erk1/2 and Akt. Accelerated proliferation was not due to TRAIL-mediated signaling but appeared to be the result of selection of previously existing, characteristically distinct cells. Moreover, responses of p53 to stimulation in the TRAIL-resistant cells appeared to be impaired.
authors.affiliation: Immunology and Oncology Unit, Newcastle Mater Misericordiae Hospital, Australia.
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Wu
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Susan
authors.initials: S
authors.lastname: Gillespie
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012878:Skin Neoplasms / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D020741:rho GTP-Binding Proteins