ETS Protein Targets in Prostate Cancer—Understanding Gene Activity that Likely Causes Up to 60 Percent of Prostate Cancer Cases Can Open Door to New Drug Development

Co-Investigator: Barbara Graves, PhD –Professor and Chair, Oncological Sciences, Senior Director for Lab Research, Huntsman Cancer Institute, University of Utah

Co-Investigator: Peter Hollenhorst, PhD –Assistant Professor, Biochemistry and Molecular Biology, School of Medicine, Indiana University

Over-expression of ETS genes, due to chromosomal fusions are the likely cause of over 40-60% of prostate cancer cases. Dr. Graves, a world leader in ETS genes in leukemia, proposes to enter the prostate cancer field and to map the DNA regions that bind ETS proteins which will in turn help to define the downstream cancer causing factors. This proposal intends to employ state-of-the-art molecular biology biotechnologies. It also recruits into prostate cancer research one of the original leading scientists studying ETS genes prior to their discovery in prostate cancer at the University of Michigan. These studies could represent the first step in discovering new medicines that could interrupt carcinogenesis of the prostate and progression of prostate cancer that occurs via ETS genes.

Progress Report:

Transcription factors are a class of proteins that bind to DNA and regulate the expression of genes involved in normal and malignant cellular processes. One family of transcription factors, ETS factors, is highly expressed in over 50% of prostate cancers due to chromosome rearrangements and is thought to be a cause of the disease. Drs. Graves and Hollenhorst identified a subset of genes that change in response ETS factor activity in prostate cancer cells. They define these genes as a “cancer signature” because many are responsible for stimulating cancer cell invasion and proliferation. These findings help explain how ETS factors are involved in the initiation and progression of prostate cancer and may provide new directions for discovery of new medicines. Drs. Graves and Hollenhorst will continue their prostate cancer research with other sources of funding including the National Institutes of Health and the Department of Defense Prostate Cancer Research Program.