Description: Estrogen plays an important physiological role in the development and function of numerous tissues. However, estrogen can also have an impact on pathological conditions, such as breast cancer and osteoporosis. Estrogen acts through its nuclear receptors, estrogen receptor a and b (ER a and ER b ), to regulate transcription of target genes. How ER activity is regulated in pathological conditions is the focus of my lab. One possible modulator of ER activity is inflammation, a process involved in many of the same diseases as estrogen. While in many cases estrogen has an anti-inflammatory effect, we have found that estrogen and inflammatory cytokines can act together to regulate expression of specific genes in a synergistic manner. Many of these genes have the potential to alter breast tumor progression and response to therapy. We are currently using molecular, cellular and translational approaches to uncover how estrogen and cytokines interact to influence breast cancer. In addition, we are exploring whether these same mechanisms may underlie estrogen action in other tissue types and diseases.
Publications:
Frasor, J., Gaspar, C. A., Donnelly, K. M., Gibori, G., and Fazleabas, A. T. Expression of prolactin and its receptor in the baboon uterus during the menstrual cycle and pregnancy. J Clin Endocrinol Metab, 84: 3344-3350, 1999.
Frasor, J., Barkai, U., Zhong, L., Fazleabas, A. T., and Gibori, G. PRL-induced ERalpha gene expression is mediated by Janus kinase 2 (Jak2) while signal transducer and activator of transcription 5b (Stat5b) phosphorylation involves Jak2 and a second tyrosine kinase. Mol Endocrinol, 15: 1941-1952, 2001.
Frasor, J., Park, K., Byers, M., Telleria, C., Kitamura, T., Yu-Lee, L. Y., Djiane, J., Park-Sarge, O. K., and Gibori, G. Differential roles for signal transducers and activators of transcription 5a and 5b in PRL stimulation of ERalpha and ERbeta transcription. Mol Endocrinol, 15: 2172-2181, 2001.
Frasor, J., Barnett, D. H., Danes, J. M., Hess, R., Parlow, A. F., and Katzenellenbogen, B. S. Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology, 144: 3159-3166, 2003.
Frasor, J., Danes, J. M., Komm, B., Chang, K. C., Lyttle, C. R., and Katzenellenbogen, B. S. Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology, 144: 4562-4574, 2003.
Rajendran, R. R., Nye, A. C., Frasor, J., Balsara, R. D., Martini, P. G., and Katzenellenbogen, B. S. Regulation of nuclear receptor transcriptional activity by a novel DEAD box RNA helicase (DP97). J Biol Chem, 278: 4628-4638, 2003.
Frasor, J., Stossi, F., Danes, J. M., Komm, B., Lyttle, C. R., and Katzenellenbogen, B. S. Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells. Cancer Res, 64: 1522-1533, 2004.
Stossi, F., Barnett, D. H., Frasor, J., Komm, B., Lyttle, C. R., and Katzenellenbogen, B. S. Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteosarcoma cells: distinct and common target genes for these receptors. Endocrinology, 145: 3473-3486, 2004.
Frasor, J., Danes, J. M., Funk, C. C., and Katzenellenbogen, B. S. Estrogen down-regulation of the corepressor N-CoR: mechanism and implications for estrogen derepression of N-CoR-regulated genes. Proc Natl Acad Sci U S A, 102: 13153-13157, 2005.
Rai, D., Frolova, A., Frasor, J., Carpenter, A. E., and Katzenellenbogen, B. S. Distinctive actions of membrane-targeted versus nuclear localized estrogen receptors in breast cancer cells. Mol Endocrinol, 19: 1606-1617, 2005.
Chang, E. C., Frasor, J., Komm, B., and Katzenellenbogen, B. S. Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells. Endocrinology, 147: 4831-4842, 2006.
Frasor, J., Chang, E. C., Komm, B., Lin, C. Y., Vega, V. B., Liu, E. T., Miller, L. D., Smeds, J., Bergh, J., and Katzenellenbogen, B. S. Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res, 66: 7334-7340, 2006.
Stender, J. D., Frasor, J. , Komm, B., Chang, K. C., Kraus, W. L., Katzenellenbogen, B. S. Estrogen regulated gene networks in human breast cancer cells: Involvement of E2F1 in the regulation of cell proliferation. Mol Endocrinol, 21 : 2112-2123, 2007.
Send email to Dr. Jonna Frasor
09/10/07