Benita S. Katzenellenbogen, PhD
Swanlund Professor, Department of Molecular and Integrative Physiology, Cell and Structural Biology
University of Illinois at Urbana-Champaign Champaign, IL

Approximately 70% of breast cancers are positive for estrogen receptor at diagnosis, and these patients often benefit from endocrine therapies, either treatment with antiestrogens such as tamoxifen or aromatase inhibitors such as letrozole, which block estrogen stimulation of these cancers by inhibiting the estrogen receptor. The effectiveness of endocrine therapies is often lost with time, however, because the tumor cells become resistant. Dr. Katzenellenbogen and her research group have shown that effective endocrine therapy involves integration of estrogen receptor actions both in the nucleus and outside of the nucleus of breast cancer cells, and that resistance involves increased activity of kinases and growth factors that work along with the protein 14-3-3ζ(zeta) to increase tumor cell growth and survival. Preliminary studies indicate that high levels of the 14-3-3ζ protein are associated with tumors that show a poor clinical outcome on endocrine therapy. Further, high levels of this protein bypass the blockade of estrogen receptor action by endocrine therapies. These results suggest that targeting 14-3-3ζ could be a useful approach for enhancing and prolonging the effectiveness of endocrine therapies.