title: c-Cbl shRNA-expressing adenovirus sensitizes TRAIL-induced apoptosis in prostate cancer DU-145 through increases of DR4/5.
abstract: We previously demonstrated that the downregulation of Casitas B-lineage lymphoma (c-Cbl) can sensitize tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in two different ways. One way is to block the rapid degradation of TRAIL receptors, which can sustain TRAIL-induced apoptosis for a long time. Here, we designed a replication-defective adenovirus expressing the short hairpin RNA (shRNA) against c-Cbl to test the possibility of developing a cancer gene therapy that can act as a sensitizer of TRAIL. As expected from the results of our previous study that used a stable cell line with downregulated c-Cbl, infection with the c-Cbl shRNA-expressing adenovirus led to an increase in the death receptor 4 (DR4) and DR5 levels, which is known to be a cause for the increase of TRAIL-induced apoptosis. In conclusion, we demonstrated that c-Cbl shRNA-expressing adenovirus is able to sensitize TRAIL-induced apoptosis in vivo as well as in vitro.
authors.affiliation: Institute for Cancer Research, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.forename: J J
authors.initials: JJ
authors.lastname: Song
mesh_terms: D000256:Adenoviridae; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D050721:Proto-Oncogene Proteins c-cbl / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human