title: Bcl-xS enhances adenoviral vector-induced apoptosis in neuroblastoma cells.
abstract: bcl-x is a member of the bcl-2 family of genes and by alternative splicing gives rise to two distinct mRNAs: bcl-xL and bcl-xS. We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-xL is expressed and functions to inhibit chemotherapy-induced apoptosis. However, none of the NB cell lines expressed Bcl-xS. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. A panel of NB cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) were infected with either a bcl-xS adenovirus (pAdRSV-bcl-xS) or a control virus (pAdRSV-lac-z). NB cells showed loss of viability with both viruses, although the bcl-xS virus was most toxic. Importantly, infection with the bcl-xS adenovirus resulted in rapid loss of cell viability, DNA fragmentation, and morphological features of apoptosis even in NB cells transfected to overexpress Bcl-2 and Bcl-xL. These findings suggest that deregulated expression of Bcl-xS using an adenovirus may provide a novel mechanism for initiating cell death in tumors that express Bcl-2 or Bcl-xL.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor 48109-0684, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Dole
authors.forename: M F
authors.initials: MF
authors.lastname: Clarke
authors.forename: P
authors.initials: P
authors.lastname: Holman
authors.forename: M
authors.initials: M
authors.lastname: Benedict
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Jasty
authors.forename: P
authors.initials: P
authors.lastname: Eipers
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: C
authors.initials: C
authors.lastname: Rode
authors.forename: C
authors.initials: C
authors.lastname: Bloch
authors.lastname: Nuñez
authors.forename: V P
authors.initials: VP
authors.lastname: Castle
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein