Estrogen Receptor Inhibition of kappaB Activity in Breast Cancer
Abstract
Estrogen receptor-alpha (ER) mediated inhibition of NF-kB contributes to the anti-inflammatory and protective effects of estrogen in bone, cardiovasculature, and perhaps breast cancer. Cross talk could be caused by direct or indirect association of these transcription factors, or by competition for other components of the transcriptional apparatus. In order to distinguish among these possibilities, we identified clonal variants of ER(+) MCF-7 breast cancer cells that either do (MCF-7 SI), or do not (MCF-SS) display ER mediated inhibition of NF-kB transcriptional activity. Transient transfection of various coactivators into the MCF-7 SS cells revealed that only CBP was able to promote an inhibitory effect of estradiol on NF-kB activity. Western Blot analysis showed that CBP protein levels were reduced in this cell line relative to the MCF-7 SS cells. Both immunofluorescent microscopy and co- immunoprecipitation showed an association between ER and NF-kB in the MCF-SS cells. CBP also immunprecipitated with ER and NF-kB in these cells. Gel shift analysis showed that estrogen treatment had no effect on the TNF-alpha induced DNA binding capability of NF-kB, suggesting that other mechanisms must be involved. ER binding to the CH/3 domain of CBP may be crucial to this effect.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407396
Entities
People
- Geoffrey L Greene
- Kendall W Nettles
Organizations
- University of Chicago