title: Inhibition of JNK-1 by small interfering RNA induces apoptotic signaling             in PC-3 prostate cancer cells.
abstract: Previous studies have shown that c-Jun-N-terminal kinase-1 (JNK-1) is involved             in the transformation of primary fibroblasts and plays a role in tumor cell growth.             A number of observations suggest that JNK-1 is a growth promoting factor in prostate             cancer cells and blocking its function may induce apoptosis. To test this further,             we used a small interfering RNA (siRNA) against JNK-1 mRNA that efficiently inhibits             JNK-1 expression in the prostate cancer cell line, PC-3. The application of siRNA             against JNK-1 decreased the expression of JNK-1 and affected the expression of             p21, XIAP and Bcl-2, but had no effect on the expression of VEGF. In contrast,             a control scramble siRNA did not affect the expression of the above indicated             proteins. The downregulation of JNK-1 expression at both the mRNA and protein             levels was detected by reverse transcription-polymerase chain reaction (RT-PCR)             and western blot analysis. Cell proliferation inhibition rates were determined             by the MTT assay. The effect of JNK-1-siRNA on cell cycle distribution and cell             apoptosis was determined by flow cytometry, DNA fragmentation and caspase activity.             Our data showed that siRNA against JNK-1 mRNA, could efficiently suppress the             expression of JNK-1 in PC-3 cells. After 5 days of transfection, the cell death             rate was 52%, the apoptotic rate 26% and the viability rate 22%. In conclusion,             downregulation of JNK-1 expression by siRNA against JNK-1 mRNA induces apoptotic             signaling in prostate cancer PC-3 cells. The use of siRNA against JNK-1 as a novel             approach to cancer therapy deserves further investigation.
authors: Biomedical Experimental Laboratory, Faculty of Sciences, University of Tarapaca, Arica, Chile. eparra@uta.cl
authors: Eduardo
authors: E
authors: Parra
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D034741:RNA, Small Interfering; D048055:Mitogen-Activated Protein Kinase 8