Dose-dependent activation of p21WAF1 transcription by all-trans-acid in cervical squamous carcinoma cells

Istvan Arany, William E. Whitehead, Istvan A. Ember, Stephen K. Tyring

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

SiHa cervical squamous carcinoma cells were resistant to ATRA-induced growth inhibitory effect at a physiological dose (10-6 M), but responsive at a pharmacological dose (10-4 M). The observed growth arrest was associated with increased levels of the interferon regulatory factor-1 (IRF-1). IRF-1 is a known inhibitor of cell growth, and thus our aim was to identify the downstream target of this growth inhibitory function. We found that, as with the induction of IRF-1, levels of p21WAF1 were similarly dose-dependently induced by ATRA. Semiquantitative RT-PCR, Western blotting, gel-shift analysis (EMSA), antisense gene expression and application of a STAT1-knockout cell line demonstrated that activation of the p21WAF1 gene was IRF-1- and STAT1-dependent. We concluded that activation of STAT1 and IRF-1 is crucial for the growth inhibitory action of ATRA, which is associated with the activation of p21WAF1. These results might be useful in chemoprevention of cervical cancers.

Original languageEnglish (US)
Pages (from-to)495-497
Number of pages3
JournalAnticancer Research
Volume23
Issue number1 A
StatePublished - Jan 2003
Externally publishedYes

Keywords

  • IRF-1
  • P21WAF1
  • Retinoids
  • STAT1
  • Transcription

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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