Affordable Access

deepdyve-link
Publisher Website

p21 expression is induced by activation of nuclear nerve growth factor-induced Balpha (Nur77) in pancreatic cancer cells.

Authors
  • Lee, Syng-Ook
  • Chintharlapalli, Sudhakar
  • Liu, Shengxi
  • Papineni, Sabitha
  • Cho, Sung Dae
  • Yoon, Kyungsil
  • Safe, Stephen
Type
Published Article
Journal
Molecular Cancer Research
Publisher
American Association for Cancer Research
Publication Date
Jul 01, 2009
Volume
7
Issue
7
Pages
1169–1178
Identifiers
DOI: 10.1158/1541-7786.MCR-08-0473
PMID: 19584258
Source
Medline
License
Unknown

Abstract

1,1-Bis(3'-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH3) activates the orphan receptor nerve growth factor-induced Balpha (Nur77) in cancer cells, and in this study, DIM-C-pPhOCH3 decreased Panc1 pancreatic cancer cell survival and arrested cells in G0-G1. These responses were accompanied by induction of the cyclin-dependent kinase inhibitor p21 in pancreatic cancer cells. Mechanistic studies showed that induction of p21 mRNA and protein by DIM-C-pPhOCH3 was Nur77 dependent but did not depend on Krüppel-like factor 4, which was also induced by DIM-C-pPhOCH3. Activation of p21 promoter constructs by DIM-C-pPhOCH3 required the GC-rich proximal region of the promoter, and results of RNA interference studies showed that Nur77-dependent activation of the p21 promoter involved interactions with Sp1 and Sp4 but not Sp3. Interactions of Nur77 with the p21 promoter in Panc1 cells treated with DIM-C-pPhOCH3 were also confirmed in chromatin immunoprecipitation assays. These data show that activation of nuclear Nur77 results in a novel pathway for induction of p21, which is independent of Nur77 response elements but dependent on Sp proteins bound to the GC-rich proximal region of the p21 promoter.

Report this publication

Statistics

Seen <100 times