Single Chain Antibodies as Estrogen Receptor Repressors in Breast Cancer
Abstract
Estrogen<dependent growth and metastasis of breast cancers Is mediated through the estrogen receptor (ER). The objective of these studies is to produce identify and demonstrate the utility of single chain antibodies (scFv) that interfere with ER action. These scFv are derived from the DNA binding domain (DBD) of the ER such that binding of a scFv to the ER DBD would prevent the interaction of the ER with estrogen response elements in the promoter of estrogen responsive genes. The estrogen dependent transcription of such genes results in the proliferation of breast cancer cells. To date several low affinity scFv have been developed. However difficulties in obtaining bacterial expression and correct folding of the scFV have been encountered. Optimizing the expression of scFv is now primarily a bacteriological problem as opposed to providing direct train in breast cancer research. I have therefore also begun to study the promoter of 1-9: an estrogen inducible inhibitor of granzyme B mediated apoptosis. Studying this gene will provide further insight into how breast cancer cells evade immune attack. I have found that the promoter of this gene contains a unique estrogen responsive unit that is capable of binding ER in both gel shift assays and DNAse I footprinting.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADB266030
Entities
People
- David J. Shapiro
- Sacha S. Krieg
Organizations
- University of Illinois Urbana–Champaign