The Role of AIB1 in Estrogen-Dependent Breast Tumor Cell Growth
Abstract
AlEl, a p16O coactivator, binds to estrogen receptor (ER) and increases estrogen-dependent transcription. It is overexpressed in 64% of primary breast tumors. We hypothesize that genes required for estrogen-dependent growth utilize AlEl for their transcription. Our hypothesis predicts that decreasing A1B1 should inhibit estrogen-dependent growth and transcription. Our experimental goal was to design inhibitors to AlEl, introduce them into MCF-7 cells, and assay cell proliferation and progesterone receptor (PgR) expression as end-points. We designed two types of inhibitors. The first was a small polypeptide that contained the 11 amino acids of the HTV TAT protein that have been shown to transduce proteins into cells, and the 19 amino acids from the AlEl LXXLL box 2 that has been shown to bind to ER. The idea was that this polypeptide would compete with the endogenous, full-length AlEl for binding to ER and thereby disrupt function. However, this polypeptide had no affect on estrogen-dependent growth or PgR expression. We have created MCE-7 Tet-Off cell lines and are stably transfecting a second inhibitor under a TEE- promoter that contains all three nuclear receptor interaction boxes of the A1Bl. Affects on estrogen-dependent growth and transcription in these cells are not yet known for this inhibitor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408992
Entities
People
- Fern E. Murdoch
Organizations
- University of Wisconsin–Madison