Sex steroid receptors in skeletal differentiation and epithelial neoplasia: is tissue‐specific intervention possible? |
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| Authors: | John A. Copland Melinda Sheffield‐Moore Nina Koldzic‐Zivanovic Sean Gentry George Lamprou Fotini Tzortzatou‐Stathopoulou Vassilis Zoumpourlis Randall J. Urban Spiros A. Vlahopoulos |
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| Affiliation: | 1. Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL, USA;2. Division of Endocrinology, Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA;3. School of Pharmacy, University of Charleston, Charleston, VA, USA;4. Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA;5. 1st Department of Pediatrics, University of Athens, Thivon and Levadias, Athens, Greece;6. Biomedical Applications, National Hellenic Research Foundation, Athens, Greece |
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| Abstract: | Sex steroids, through their receptors, have potent effects on the signal pathways involved in osteogenic or myogenic differentiation. However, a considerable segment of those signal pathways has a prominent role in epithelial neoplastic transformation. The capability to intervene locally has focused on specific ligands for the receptors. Nevertheless, many signals are mapped to interactions of steroid receptor motifs with heterologous regulatory proteins. Some of those proteins interact with the glucocorticoid receptor and other factors essential to cell fate. Interactions of steroid receptor domain motifs with heterologous proteins affect specific target pathways; consequently, manipulation of specified protein modules complexed with steroid receptors may be a next major step for enhancing molecular targeted therapeutics. In the future, intervention at specific sections of receptor primary sequence may prove therapeutically more efficient in targeting pathways of choice than ligand selectivity can be. |
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