title: Parkin induces apoptotic cell death in TNF-α-treated cervical cancer cells.
abstract: Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-α)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-α-induced cell death. TNF-α-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-α-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-α-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 220-710, Korea.
authors.forename: Kyunghong
authors.initials: K
authors.lastname: Lee
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Lee
authors.forename: Yeo Wool
authors.initials: YW
authors.lastname: Kang
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.forename: Tae Ue
authors.initials: TU
authors.lastname: Kim
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053179:Caspase 7; D053181:Caspase 8; D053453:Caspase 9