Identification of a functional peroxisome proliferator activated receptor response element in the 3' untranslated region of the human bcl-2 gene.

Brent D. Butts, Nhan L. Tran, Margaret M Briehl

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Peroxisome proliferator activated receptors are nuclear hormone receptors that regulate the expression of genes containing a peroxisome proliferator activated receptor response element. We report here that the human bcl-2 gene contains a functional peroxisome proliferator activated receptor response element in the 3' untranslated region. Peroxisome proliferator activated receptor gamma bound the human bcl-2 peroxisome proliferator activated receptor response element in gel shift assays and co-transfection of this receptor led to increased luciferase activity from a reporter plasmid containing the human bcl-2 peroxisome proliferator activated receptor response element. Examination of peroxisome proliferator activated receptor gamma-transfected cells demonstrated an increased amount of bcl-2 message compared to empty vector-transfected cells. Confocal analyses confirmed that more Bcl-2 protein was present in peroxisome proliferator activated receptor gamma-transfected cells compared to control-transfected cells. The functionality of the increased Bcl-2 protein was examined using resistance to bile salt-induced apoptosis as the endpoint. Peroxisome proliferator activated receptor gamma-transfected cells were almost twice as resistant as control-transfected cells. These data show that PPARgamma can mediate transcription of bcl-2, resulting in an increase in Bcl-2 protein and protection from apoptosis. We discuss these findings with regards to their potential implications for colon carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1305-1310
Number of pages6
JournalInternational Journal of Oncology
Volume24
Issue number5
Publication statusPublished - May 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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