Welcome to the University of Colorado School of Medicine on the Anschutz Medical Campus. We are a Top Ten Medical School in primary care, pediatrics, family medicine and rural medicine, and offer physical therapy and physician assistant programs.

Research in our laboratory focuses on the actions of women's ovarian hormones, estradiol and progesterone, and their role in breast cancer. These hormones activate intranuclear receptors that regulate gene transcription. In breast cancers, estrogen (ER) and progesterone (PR) receptors control tumor development and growth, they are markers of hormone dependence and tumor aggressiveness, and they are targets for treatments with antiestrogens, aromatase inhibitors and progestins. The lab consists of approximately 15 collaborating investigators with appointments as junior faculty, postdoctoral and clinical fellows, graduate and medical students, and research assistants. The research in breast cancer ranges from basic molecular biology of receptor action in transcription, to cell and tumor biology, role of hormones in metastasis, and translational studies.

Nuclear Receptors and Transcription. 1. To understand why two forms of PR - the PR-A and PR-B isoforms - have different transcriptional activites and different roles in breast cancer prognosis, tumor growth, and response to treatments, we have undertaken detailed protein structural analyses of the two receptors focused on the large N-terminal region. To this end the proteins are overexpressed in insect cells, purified to homogeneity, and analyzed by a variety of protein structural and biophysical methods. 2. Studies also include detailed N-terminal mapping studies involving site-specific and random mutagenesis of regions unique to PR-B, and studies addressing the role of post-transcriptional protein modifications, like phosphorylation and SUMOylation, on receptor function. 3. N-terminal binding, transcriptional coregulatory proteins are being identified.

Cell Biology. 4. We take advantage of the power of expression profiling to define genes involved in estrogen and progesterone signaling, cross-talk between the two receptor systems, tumor metastasis, etc. 5. Inducible human breast cancer cell models have been developed in which receptors are "off" until switched "on. These are used to refine expression analyses, to probe for ligand-independent effects of receptors, and to analyze differential receptor effects on tumor response to hormonal and chemotherapeutic agents including effects of taxanes.

Tumor Biology. 6. Hormones and breast cancer growth. Different human breast cancer cell lines with varying ER and/or PR content are grown as hormone dependent tumors in nude mice and analyzed for the role of receptors, hormones and hormonal treatments, on tumor growth and regression. 7. Breast cancer metastasis. Powerful new models have been created using highly green and red fluorescent tumor cells that allow accurate tracking of the spread of cells out of primary tumor sites to metastatic sites in the nude mice. Expression profiling and other studies address mechanisms for hormone regulation of metastases.

Translational. 8. In collaborative studies, the observations and hypotheses derived from basic research studies are extended into translational research using tumors taken from patients. 9. Patient tumor samples are also used to analyze the role of tumor cells in altering the tumor microenvironment and stromal/epithelial cell interactions.