Interaction Between Estrogen Receptor Beta and the Transforming Growth Factor Beta Signaling Cascade in Human Breast Tissue
Abstract
Recent evidence has suggested that cross-talk between the TCFbeta and ER signaling pathways exist. Data from our laboratory suggests that although a physical interaction between ER and Smad3, a downstream signaling protein of the TGFbeta pathway, does not exist, a functional interaction is present. ERalpha and ERbeta inhibit Smad3 transcription on the TGFbeta reporter plasmid p3TP-lux in a ligand-dependent manner and this inhibition may be suppressed and subsequently reversed by the anti-estrogens 4-OH-tamoxifen and ICI 182,780. As both ERalpha and Smad3 interact with members of the Apl family and since the p3TP-lux promoter has three Apl binding sites, we next sought to examine whether Apl factors may be limiting factors in Smad3 transcription on p3TP-lux. Results suggest that overexpression of c-Jun but not c-Fos was able to reverse the effect of ERalpha on Smad3 transcription in Cosl cells. Our results suggest that Apl factors may be important in the regulation of TGFbeta signaling by ER. Experiments are currently underway to determine if these observations are relevant in a breast tumor cell model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA425903
Entities
People
- Leigh C. Murphy
- Tracy C. Cherlet
Organizations
- University of Manitoba