Description: Most published data on human ER-ß function/signaling have been derived from studies on ER-ß1, the originally cloned sequence. However, there are five splice-variants of ER-ß that have until recently been poorly characterized. Dr. Shuk-Mei Ho and colleagues at the University of Cincinnati isolated and expressed the full length cDNA’s for ER-ß2, ER-ß4 and ER-ß5 and examined ligand binding, dimerization, transactivation and coactivator binding. In addition, in silico modeling was performed to examine structural characteristics.
Dr. Ho’s work demonstrated that ER-ß1 is the only fully functional isoform and that ER-ß2, ER-ß4 and ER-ß5 do not have innate activities in their homodimeric forms. However, ER-ß2, ER-ß4 and ER-ß5 can heterodimerize with ER-ß1 and enhance ER-ß1- induced transactivation in a ligand dependent manner.Dr. Ho’s work provides the first evidence that ER-ß1 prefers to form heterodimers with its isoforms and the process is likely dependent on ligand type.
Her work also revealed pronounced differences in expression of ER-ß isoforms in normal human cell lines/tissues and that prostate, ovarian and breast cancer cell lines have distinct expression profiles relative to the corresponding normal cell lines/tissues. This data suggests that tissue responsiveness is determined by isoform expression and that ER-ß heterodimers may provide specific, and as yet, unexplored, targets for therapeutic intervention in a variety of ER-ß related diseases.The University of Cincinnati is seeking industry partners for the development therapeutics/diagnostics related to ER-ß isoforms. A patent application has been filed.
For more information please contact Ellen Monson at 513-558-5274 or geoffrey.pinski@uc.edu
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