CRE Activation in Antiestrogen Resistance
Abstract
HXBP-1, a basic leucine zipper protein (bZIP), is transcription factor that belongs to the activating transcription factor/cAMP response element-binding protein (ATFICRE) family of transcription factors and can bind to and activate the cyclic AMP response elements (CREs). In our previous studies, serial analysis of gene expression has shown that hXBP-1 may contribute to antiestrogen resistance in human breast cancer cells. In antiestrogen resistant cells CRE-regulated transcription (promoter-reporter assay) activity is increased 4-fold. Thus, the purpose of our experiments is to determine whether hXBP-1/CRE contribute to antiestrogen resistance by over-expressing hXBP-1 in cell lines that are sensitive to antiestrogen. MCF7 cells were transfected with hXBP-1 cDNA. Western blotting showed increased expression in transfectants; activity of this protein was confirmed in a promoter - reporter assay measuring luciferase activity as an indicator of CRE activation. Preliminary data show that MCF7 cells over-expressing hXBP-1, when exposed to antiestrogens such as 4-hydroxy- Tamoxifen and ICI 182, 780, are able to survive the growth inhibitory effects of these antiestrogens when compared to the parental MCF7 cells. Similar observations were observed when both cell types were grown in media devoid of estrogen (E2).
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA428088
Entities
People
- Bianca P. Gomez
- Robert Clarke
Organizations
- Georgetown University