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 language | English (US) |
|---|---|
| Pages (from-to) | 495-497 |
| Number of pages | 3 |
| Journal | Anticancer Research |
| Volume | 23 |
| Issue number | 1 A |
| State | Published - Jan 2003 |
Keywords
- IRF-1
- P21WAF1
- Retinoids
- STAT1
- Transcription
ASJC Scopus subject areas
- Oncology
- Cancer Research