Splicing Variants of Estrogen Receptor in Breast Cancer
Abstract
Progress reported for year 4 of this award includes: (1) an analysis of ER-alpha mRNA variants in two cell lines (TG-1 and TG-3c) from the MCF10AT series (a model for preneoplastic breast disease), (2) PCR analysis of ER-alpha mRNA in M13 SV1 and R(sub 2)N(sub 1) cells (SV40 immortalized normal human breast epithelial lines developed as a model for breast stem cells), and (3) continued characterization of selected ER-alpha splicing variants, focusing on non-canonical estrogen response elements (EREs). The findings extend our work to include two new model systems for premalignant breast disease. In both models, a diverse array of splicing variants are seen at the RNA level, but the major variants differ compared with the MCF-7 system. We continue to investigate the significance of these findings by analyzing the behavior of transfected reporter plasmids in the TG-1, TG-3c, and M13 cell lines. Our analysis of the ability of ER-alpha splicing variants to modulate gene expression via non-classical (ERE-independent) pathways has also progressed. Data from transfection studies exploring the behavior of selected splicing variants on four reporter constructs that lack consensus EREs are summarized. A variety of behaviors are observed, including reporters that are activated primarily by ER-delta-E3, primarily by ER-delta-E5, or by both. These studies provide the first convincing evidence that ER-alpha variants are able to mediate positive regulation of gene expression on a subset of genes that contain non-canonical hormone response elements.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA366564
Entities
People
- Richard J. Miksicek
Organizations
- State University of New York