title: No compensation in VEGF expression follows antisense suppression of BCL-2 activity.
abstract: Antisense oligonucleotides (oligos) have been employed against prostate cancer models targeting growth-regulatory proteins, and at least one oligo (against bcl-2) has reached clinical trial. We previously found that, in LNCaP cells, mono- and bispecific oligos, which comparably suppressed the expression of bcl-2, compensated with suppression of caspase-3 (apoptosis promoter) activity, and enhanced the expression of the androgen receptor (AR) and its p300 and IL-6 co-activators. In addition, prostate-specific membrane antigen (PSMA) and (possibly its regulator) interferon (IFN) were elevated. A total of 14 proteins distributed between regulators of apoptosis, androgen regulation, differentiation antigens and autocrine-mediated growth have previously been examined. We extend these findings to include vascular endothelial growth factor (VEGF), a promoter of angiogenesis, which is not significantly altered through compensation, and therefore would not need additional regulation for suppressive bcl-2 therapy to be effective (like caspase-3).
authors.affiliation: Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, IL 60612, USA. DrMarv@Prodigy.net
authors.forename: Marvin
authors.initials: M
authors.lastname: Rubenstein
authors.forename: Courtney M P
authors.initials: CM
authors.lastname: Hollowell
authors.forename: Patrick
authors.initials: P
authors.lastname: Guinan
mesh_terms: D000954:Antigens, Surface; D017209:Apoptosis; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; D042461:Vascular Endothelial Growth Factor A; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II