Compensatory and non-compensatory effects on protein expression following BCL-2 suppression by antisense oligonucleotides

Marvin Rubenstein*, Courtney M P Hollowell, Patrick Guinan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth regulatory proteins. In LNCaP cells, we evaluated both monospecific and bispecific oligos that targeted and comparably suppressed the expression of bcl-2, an apoptosis inhibitory protein. Cells compensated with both suppressed caspase-3 (an apoptosis promoter) activity, and an enhancement of both androgen receptor (AR) and p300 expression. This suggests that a progression to increased androgen sensitivity accompanies bcl-2 suppression, in this tumor line. To further evaluate mechanisms of adaptation, we now evaluate the effects upon the expression of insulin-like growth factor (IGF1) and another AR coactivator, IL-4, thought to increase prostate cancer growth. IGF1 expression was not significantly altered suggesting this pathway need not be regulated when bcl-2 directed gene therapy is employed. In contrast to increased AR and p300 expression that compensated for bcl-2 suppression, the AR coactivator IL-4 expression was not increased, suggesting no role in any increased androgen sensitivity.

Original languageEnglish (US)
Pages (from-to)2284-2290
Number of pages7
JournalMedical Oncology
Volume29
Issue number3
DOIs
StatePublished - Sep 2012

Keywords

  • Antisense
  • Bcl-2
  • Prostate cancer
  • Therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Compensatory and non-compensatory effects on protein expression following BCL-2 suppression by antisense oligonucleotides'. Together they form a unique fingerprint.

Cite this