Splicing Variants of the Estrogen Receptor in Breast Cancer
Abstract
Progress reported for year 3 of this award includes: (1) completion of a thorough analysis of ER-alpha mRNA variants in MCF-7 cells, (2) the analysis of ER-alpha variants in an invasive ductal carcinoma specimen characterized by a discordant ER status, (3) continued characterization of the functional properties of six major ER-alpha splicing variants, and (4) the generation and preliminary characterization of cell lines that stably express ERdeltaE5. Our findings reconfirm that the estrogen-responsive MCF-7 breast epithelial cell line expresses a heterogeneous array of ER-alpha mRNA transcripts, less than half of which would encode a full-length, transcriptionally functional receptor. The most abundant variant present in MCF-7 cells is ER delta E7. Occasional breast tumors can display an even more extreme pattern of variant ER-alpha mRNA expression. There is diminishing evidence to support the contention that ER delta E5 represents a constitutively active variant, Indeed, ER delta E5 is essentially devoid of DNA-binding activity and transient and stable expression experiments indicate that it has little if any positive transcriptional activity. Rather, like ER delta E3, the ER delta E5 variant can act as a dominant inhibitory receptor when it is co-expressed with wt ER-alpha. Future work will address the potential of ER-alpha splicing variants to modulate the expression of estrogen responsive genes via non-classical (DNA-independent) pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA374095
Entities
People
- Richard J. Miksicek
Organizations
- State University of New York