A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-κB or ODC transactivation

Hsin Sheng Yang, Aaron P. Jansen, Rajalakshmi Nair, Keiichi Shibahara, Ajit K. Verma, Joan L. Cmarik, Nancy H. Colburn

Research output: Contribution to journalArticlepeer-review

172 Scopus citations

Abstract

Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Over-expression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression of Pdcd4 protein is sufficient to suppress neoplastic transformation. To determine whether Pdcd4 suppresses neoplastic transformation through inhibiting known transformation required events, we examined the possibility that pdcd4 inhibited the activation of AP-1 or NF-κB dependent transcription or of ornithine decarboxylase (ODC) activity. Activation of AP-1-dependent transcriptional activity was inhibited by pdcd4 expression in a concentration dependent manner. In contrast, Pdcd4 slightly increased NF-κB-dependent transcription and did not alter ODC enzymatic activity. Previous studies suggested that activation of AP-1 was required for P + cell transformation as well as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a transformation suppressor, possibly through inhibiting AP-1 activation in combination with other factors such as enhancing NF-κB activation. Pdcd4 may thus constitute a useful molecular target for cancer prevention.

Original languageEnglish
Pages (from-to)669-676
Number of pages8
JournalOncogene
Volume20
Issue number6
DOIs
StatePublished - Feb 8 2001

Keywords

  • AP-1
  • NF-κB
  • Pdcd4
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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