> CPDR News
USU’s Center for Prostate Disease Research Provides New Insights Into Common Alterations of ERG Oncogene in Prostate Cancer
October 6, 2008
BETHESDA, Md. — In the past three years, ground-breaking discoveries in the prostate cancer field have highlighted that alterations of ETS related genes (predominantly ERG), as a result of a fusion between male hormone receptor regulated gene promoters (predominantly TMPRSS2) and ETS transcription factors, represent one of the most common oncogenic defects in prostate cancer. Researchers at the Center for Prostate Disease Research (CPDR) at the Uniformed Services University of the Health Sciences (USU) had originally shown frequent overexpression (60-70%) of the ETS related gene ERG in the epithelial cell transcriptome of prostate cancers. In their continued quest to understand the functional role and clinical utility of ERG alterations in prostate cancer, CPDR researchers have now defined new features of ERG function and expression which will further enhance the potential of ERG as promising biomarker and therapeutic target for prostate cancer.
Using cell culture and animal models and prostate cancer specimens from patients, the multi-disciplinary group co-led by Dr.Shiv Srivastava, Dr. David G. McLeod, Dr. Isabell A. Sesterhenn and Dr. Albert Dobi shows that inhibiting ERG expression in prostate tumor cells induces markers of prostate differentiation and inhibits tumor cell growth in mice. This study also highlights the role of the C-MYC oncogene in mediating ERG functions in prostate cancer cells. Taken together, these novel findings strongly implicate causal roles of ERG in prostate cancer at least in part by affecting cellular differentiation. Moreover, this study underscores promising potential of ERG and C-MYC in developing new targeted therapy for a large percentage of prostate cancers with ERG overexpression (60-70%).
The second innovative CPDR study, co-led by Dr. Shiv Srivastava, Dr. David G. McLeod, Dr. Isabell A. Sesterhenn and Dr. Gyorgy Petrovics, defines full length transcripts and proteins encoded by common TMPRSS2-ERG fusions in prostate tumors. This study for the first time has led to the discovery of two major types of ERG products (type I: full length and type II: without ETS domain) in prostate tumors. Surprisingly, they found an abundance of type II products in tumors cells. Although the functional role of the type II products is unclear, early data suggest that ratios of type I and type II products in prostate tumor cells may provide prognostic indicators for disease progression. New information from this study has promise to enhance future strategies for utilizing specific ERG products as biomarkers or as therapeutic targets. Further studies are also warranted that would address the role of specific ERG products in overall ERG functions in prostate cancer. Towards these goals the CPDR team has been recently awarded a three year grant from the DoD-Prostate Cancer Research Program.
The CPDR mission is fulfilled primarily through its three principal programs – the Clinical Research Center, the Basic Science Research Program and the National Multicenter Prostate Cancer Database– and through a robust education and training program that operates out of its Headquarters location, the Clinical Research Center, and the original laboratories at USUHS. CPDR is also committed to patient outreach, primarily through its affiliation with the WRAMC US TOO! organization and through a heavy schedule of health fairs in which it participates.
