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: Marvin Rubenstein, Courtney M P Hollowell, Patrick Guinan
• Journal: In vivo (Athens, Greece) (In Vivo) 2014 Sep-Oct Vol. 28 Issue 5 Pg. 867-70 ISSN: 1791-7549 [Electronic] Greece
• PMID: 25189901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Oligonucleotides, Antisense
• Proto-Oncogene Proteins c-bcl-2
• STAT3 Transcription Factor
• Proto-Oncogene Proteins c-akt

Topics

• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Humans
• Oligonucleotides, Antisense (administration & dosage, genetics)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• STAT3 Transcription Factor (genetics, metabolism)