CRE Activation in Antiestrogen Resistance
Abstract
HXBP-1, a basic leucine zipper protein (bZIP), is a transcription factor that belongs to the activating transcription factor/cAMP response element-binding protein (ATF/CRE) family of transcription factors and can bind to and activate the cyclic AMP response elements (OREs). 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 ORE-regulated transcription (promoter- reporter assay) activity is increased 4-fold. Thus, the purpose of our experiments is to determine whether hXBP-1/CRE contributes to antiestrogen resistance by overexpressing hXBP-1 in cell lines that are sensitive to antiestrogens. T-47D and MCF-7 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 ORE activation. Our data show that T-47D and MCF-7 cells over-expressing hXBP-1, when exposed to antiestrogens such as 4-hydroxy- Tamoxifen (TAM) and 101182, 780 (FAS), are able to survive the growth inhibitory effects of these antiestrogens when compared to the empty vector controls of T-47D and MCF-7 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, 2005
- Accession Number
- ADA444660
Entities
People
- Bianca P. Gomez
- Robert Clarke
Organizations
- Georgetown University