title: A recombinant adenovirus expressing wild-type Bax induces apoptosis in prostate cancer cells independently of their Bcl-2 status and androgen sensitivity.
abstract: Using a binary co-transfection strategy of Ad/GT Bax and Ad/PGK-GV16, we have succeeded in inducing overexpression of Bax protein in three prostate cell lines (androgen-insensitive DU145 and PC3, and androgen-sensitive LNCaP). The expression of Bax protein by this system was sufficient to induce all three prostate lines to undergo apoptosis. The fact that DU145 cells which have a p53 mutation and are deficient in Bax, responded to this treatment, suggests that this effect is independent of these pathways. Initiation of the cleavage of Caspase-3 (CPP32/Yama/apopain) and PARP (poly (ADP-ribose) polymerase) by the introduction of Bax were confirmed by western blot analysis. Bcl-2 expression is relevant in the progression of prostate cancer and contributes to an androgen, apoptotic-resistant phenotype in the advanced stages. We examined stable Bcl-2 overexpressing DU145, PC3 and LNCaP cell lines as models of advanced prostate cancer. The adenoviral co-transfection system induced Bax protein expression and apoptosis even in these Bcl-2 transfected cell lines. Taken together, our results suggest that this Bax expression system might represent a useful gene therapy strategy when applied to the treatment of prostate cancer and its efficacy would be independent of the Bcl-2 status and androgen sensitivity of these cancers.
authors.affiliation: Department of Molecular Pathology, Box 89, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Honda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Spurgers
authors.forename: Bjorn T
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Lowe
authors.forename: James S
authors.initials: JS
authors.lastname: Norris
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Meyn
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonnell
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000728:Androgens / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: D000728:Androgens; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases