CRE Activation in Antiestrogen Resistance
Abstract
The over-expression of the human X-base binding protein (h-XBP- 1) and hence elevated levels of CRE transcription activator contributes to the antiestrogen resistance. Preliminary data using Western blot analysis indicates that E2 -independent but responsive breast cancer cells that are responsive to antiestrogen showed elevated hXBP- 1 protein level whereas the cell line that is resistant to antiestrogen showed a lower level of hXBP- 1 protein expression. Furthermore, a promoter-reporter assay measuring luciferase activity as an indicator of CRE activation showed that cells that are antiestrogen resistant had a four- fold increase in CRE activation when compared to the sensitive cells. HXBP-l is transcription factor that belongs to the ATF/CRE family of transcription factors and can bind to and activate the CREs (cyclic AMP response elements). It is based on this relationship that the amount of hXBP- 1 protein levels could be determined by measuring the level of CRE containing genes. In our experiments by over expressing hXBP-l using transfection we well convert sensitive cells to resistant cell. On the other hand, cell resistant to antiestrogen will become sensitive by using an antisense oligonucleotide approach. Anchorage dependent as well as anchorage independent growth responses of the respective transformed cells to antiestrogen will also be measured.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA418668
Entities
People
- Bianca P. Gomez
- Robert Clarke
Organizations
- Georgetown University