p21 Expression Is Induced by Activation of Nuclear Nerve Growth Factor–Induced Bα (Nur77) in Pancreatic Cancer Cells Academic Article uri icon


  • 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 Krppel-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.

published proceedings

  • Mol Cancer Res

author list (cited authors)

  • Lee, S., Chintharlapalli, S., Liu, S., Papineni, S., Cho, S. D., Yoon, K., & Safe, S.

citation count

  • 22

complete list of authors

  • Lee, Syng-Ook||Chintharlapalli, Sudhakar||Liu, Shengxi||Papineni, Sabitha||Cho, Sung Dae||Yoon, Kyungsil||Safe, Stephen

publication date

  • July 2009