The research emphasis is in the molecular endocrinology of the breast, uterine and ovarian carcinomas with a focus on mechanisms of action of steroid and peptide hormones involved. Clinical research is directed toward development and application of prognostic factors for improving cancer management. The following describe the projects that are currently being investigated at the Hormone Receptor Laboratory.
N-terminal Mutations of the Human Estrogen Receptor Gene-This project's goal is to develop microbial systems for expressing large quantities of full-length, highly active receptor proteins of the steroid hormone/thyroid hormone superfamily of genes. The research represents a major collaboration with the Institute of Applied Microbiology in Vienna, Austria and the University of Pennsylvania. Systematic site-directed mutation of the amino- terminus sequence of the human estrogen receptor gene alters expression and function of its protein product. A few receptor mutants exhibit superior properties for binding ligands and estrogen response elements as well as transactivation of a model gene in a yeast cell-based bio-assay. Results suggest reagent quantities of these labile regulatory proteins may be generated for structural and functional analyses. Click here to view the list of related papers.
Detection of Estrogens and Their Mimics in the Environment-One aspect involves NIH/SBIR supported research in collaboration with IA, Inc. to develop a fiber optic sensor for detecting estrogen mimics in the environment. Recombinant human estrogen receptors are used for a highly sensitive instrument for field measurements of pseudoestrogens. The second component is funded by the Veteran's Administration Center for Environmental Hazards to Reproductive Health. The specific goal of the HRL is to develop rapid screening techniques for identifying female sex-hormone mimics that may either disrupt reproduction or participate in cancer. Assessment of a compound's potential includes inhibition of hormone binding in cell-free receptor preparations, disruption of receptor association with estrogen response elements in vitro and blockade or alteration in transactivation of a reporter gene in a yeast cell-based bioassay. Click here to view the list of related papers.
Identification of Estrogen Receptor Protein Variants with Monoclonal Antibodies-Although estrogen and progestin receptors are used as prognostic factors in breast cancer management, 25-30% of patients with receptor positive cancer do not respond objectively to hormone therapies. Since estrogen receptor variants have been predicted from measurements of mRNA and gene alterations, this NIH/SBIR sponsored project is developing isoform specific monoclonal antibodies to study receptor polymorphism. Three new monoclonal antibodies recognizing epitopes in the D/E/F domains have been developed for correlating estrogen receptor molecular heterogenity with tumor pathology and clinical course. Click here to view the list of related papers.
Urokinase-type Plasminogen Activator, its Receptor and its Inhibitor-This industry funded project investigates the role of serine protease in progression of breast, colon and reproductive cancer. Preliminary evidence in the literature suggests over-expression of uPA, its receptor, uPAR and its inhibitor, PAI-1 in breast cancer is correlated with poor prognosis. The main goal is to develop reference materials and standardized assay protocols so these analytes may be evaluated in clinical cancer trials. Click here to view the list of related papers.
Characterization of Sex Hormone Receptors. Click here to view the list of related papers.