Evan T. Keller, D.V.M., Ph.D. | Institute of Gerontology

Research Associate Professor, IoG
Associate Professor
Department of Pathology
Associate Professor of Urology
Medical School

5340 CCGCB
Ann Arbor, MI 48109-0940
Tel: (734) 615-0280
Fax: (734) 936-9220
Email: etkeller@umich.edu

Prostate cancer is a disease the primarily occurs in elderly men. When prostate cancer occurs, it often is initially dependent on androgens for growth. Thus, it is treated by blocking androgen activity. However, it eventually recurs without an apparent need for androgens. This recurrent androgen-independent cancer then has a predilection to metastasize to bone. Our team is attempting to determine how prostate cancer progresses to androgen independence. We are primarily focused on molecular studies on the androgen receptor to explore this issue. Another research area our group is active in is understanding the mechanism of prostate cancer spread to bone. We look at metastasis suppressor genes, and the interactions between cancer cells and the bone tissue. We do this work in a variety of animal models. Finally, our team is attempting to define the mechanism(s) through which aging modulates gene expression. We have been primarily focused on the molecular biology of interleukin-6 (IL-6), a cytokine whose levels are increased with age in rodents and primates. To explore these mechanisms we are using a combination of in vitro molecular and cellular techniques and in vivo animal models.

Publications:

Zhang J, Dai J Smith P, Qi Y, Lin D, Strayhorn C, Mizokami A, Fu Z, and Keller ET. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone of mice. J Clin Invest, 107:1235-1244, 2001.

Zhang J, Johnston G, Stebler B, Keller ET. Oxidative stress-mediated activation of NFkB and the interleukin-6 promoter requires NF?B-inducing kinase activity. Antioxidant Redox Signaling, 3:493-504, 2001.

Smith PC and Keller ET. Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. Prostate, 48:47-53, 2001.

Lin DL, M Whitney, Z Yao, Keller ET. Interleukin-6 induces androgen receptor activity through up-regulation of receptor expression in prostate cancer cells. Clin Cancer Res, 7:1773-1781, 2001.

Evan T. Keller, Jian Zhang, Carlton R. Cooper, Peter C. Smith, Laurie K. McCauley, Kenneth J. Pienta and Russell S. Taichman. Prostate carcinoma skeletal metastases: Cross-talk between tumor and bone. Cancer Metastasis Reviews 20:333-349, 2001.

Fu Z, Dozmorov IM, Keller ET. Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells similar to that found in bone metastatic prostate cancer cells. Prostate, 51:10-20, 2002.