title: Additional compensatory mechanisms altering antisense oligonucleotide suppression of BCL2: effects upon AKT1 and STAT3.
abstract: Antisense oligonucleotides have targeted regulatory proteins in both in vivo and in vitro prostate cancer models. We evaluated mono- and bispecific oligonucleotides which targeted and comparably suppressed B-cell lymphoma-2 BCL-2 (an apoptosis-inhibitory protein) expression in LNCaP cells. These oligonucleotides were administered with lipofectin as part of a nanoparticle delivery system. Treated cells compensated by suppressing caspase-3 (an apoptosis promoter) and enhancing expression of the androgen receptor and its co-activating p300 and IL-6 proteins. This suggests a progression to increased androgen sensitivity (in LNCaP) accompanies BCL-2 suppression and a gene activation pattern associated with more advanced prostate tumors. To further evaluate compensatory mechanisms related to tumor resistance in the present study we evaluate the expressed levels of the AKT1 oncogene and STAT3 transcription factor, finding both to be enhanced.
authors.affiliation: Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, IL, U.S.A. Division of Urology, Stroger Hospital of Cook County, Chicago, IL, U.S.A. Department of Biochemistry, Rush University Medical Center, Chicago, IL, U.S.A. Department of Urology, Rush University Medical Center, Chicago, IL, U.S.A. DrMarv@Prodigy.net.
authors.forename: Marvin
authors.initials: M
authors.lastname: Rubenstein
authors.affiliation: Division of Urology, Stroger Hospital of Cook County, Chicago, IL, U.S.A.
authors.forename: Courtney M P
authors.initials: CM
authors.lastname: Hollowell
authors.affiliation: Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, IL, U.S.A. Division of Urology, Stroger Hospital of Cook County, Chicago, IL, U.S.A. Department of Urology, Rush University Medical Center, Chicago, IL, U.S.A. Department of Urology, University of Illinois at Chicago, Chicago, IL, U.S.A.
authors.forename: Patrick
authors.initials: P
authors.lastname: Guinan
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt
keywords: Antisense; BCL-2; prostate cancer; therapy