Benita S. Katzenellenbogen, PhD

Dr. Katzenellenbogen's team has studied 14-3-3Z, a protein important in breast cancer. They have found that 14-3-3Z enables tumor cells to survive and no longer respond to endocrine treatments. Importantly, they have found that the level of 14-3-3Z in breast cancers can be reduced by increasing the level of a specific microRNA, thereby restoring responsiveness to endocrine therapies.

In continuing studies, the Katzenellenbogen laboratory will develop ways to monitor the level of 14-3-3Z and a tumor suppressor-like microRNA as tumor biomarkers and explore therapeutic approaches to increase expression of this microRNA to downregulate 14-3-3Z and enhance the effectiveness of endocrine therapies in estrogen receptor positive breast cancers. They will also investigate ways to reduce the influence of 14-3-3Z by blocking proteins through which 14-3-3Z acts to promote cancer cell survival and resistance to therapies. These approaches should prove valuable in monitoring and restoring sensitivity to endocrine therapies, thereby reducing the risk of breast cancer recurrence.

Mid-year Progress: Dr. Katzenellenbogen is investigating a new dimension of endocrine therapy resistance by finding that tamoxifen up-regulates 14-3-3Z, a protein that is frequently very high in breast tumors of patients with a poor clinical response to endocrine therapy. Her research group has identified 14-3-3Z as a predictor of early time to breast cancer recurrence and a molecular target in metastatic breast cancer. Also, they have found that tamoxifen reduces microRNA-451 (miR-451), resulting in the elevation of 14-3-3Z and genes that stimulate cancer cell proliferation and metastasis. They have shown that increasing miR-451 was able to restore the beneficial effects of tamoxifen. Thus, these findings suggest that targeting 14-3-3Z and its coregulated proteins, as well as approaches that increase expression of this microRNA, should enhance the effectiveness of endocrine therapies and reduce risk of breast cancer recurrence.

Bio:
Benita Katzenellenbogen is Swanlund Professor of Physiology, Cell and Structural Biology, and director of a breast cancer research group at the University of Illinois and University of Illinois College of Medicine at Urbana-Champaign. She is an internationally known endocrinologist and cancer researcher and has been a key scientist in understanding the biology of estrogen receptors and in elucidating mechanisms by which antiestrogens and SERMs, such as Tamoxifen and Raloxifene, are effective in controlling breast cancer. The work of her research group has most recently involved the development of selective hormonal agents for breast cancer treatment and prevention.

The quality and impact of Professor Katzenellenbogen's scholarly achievements are extraordinary. Since joining the faculty of the University of Illinois in 1971, she has published over 250 research articles, has contributed 30 chapters in books, and has co-edited a text on hormone-dependent cancers.

She is the recipient of numerous awards, honors and special fellowships from governmental, private and academic institutions including the MERIT Award (1991-1999) from the National Cancer Institute at the National Institutes of Health, the Jill Rose Award for outstanding research from The Breast Cancer Research Foundation, the Ernst Oppenheimer Award and Roy O. Greep Lecture Award of The Endocrine Society, the Distinguished Scientist Award from the Susan G. Komen Breast Cancer Foundation, and the National Scholar Award from the American Association of University Women.

She is a Fellow of the American Academy of Arts and Sciences and recently served as President of The Endocrine Society, the world's largest professional society representing approximately 10,000 endocrinologists. She has been active on government scientific review panels of the National Institutes of Health and the American Cancer Society, and has served on the editorial boards of several scientific journals. She directs an active research unit that has trained over 70 graduate students and postdoctoral scientists, many of whom are leading distinguished careers in academia, governmental agencies, and the pharmaceutical/biotechnology industry.