ASCO GU 2008 - Effect Of Abberant ERG Expression On Prostate Tumorigenesis

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Men's health
Article Date: 24 Feb 2008 - 0:00 PDT

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UroToday.com - ETS transcription factors ERG and TMPRSS2 can activate or repress the expression of genes involved in various biological processes. ETS family members in cancer can result in a fusion protein that impacts cancer. A mouse model of ERG was developed. ERG aberrant expression did not promote HGPIN formation in the mouse model. He correlated this with the fact that ERG genetic arrangements are infrequently found in human HGPIN. Approximately 10% of CAP associated HGPIN will display genetic rearrangement of ERG. Whether this influences initiation or progression of CaP is under study.

Regarding the association of PTEN loss and ERG genetic rearrangements, they are not mutually exclusive genetic events, he said. He crossed PTEN +/- mice with ERG mice. They found this promoted tumor acceleration and progression in the crossed mice. ERG promoted tumor progression without effect on proliferation. PTEN loss and ERG genetic rearrangement are frequent concomitant events in human CaP. He reported that ERG FISH positivity occurred in 8-15% of human samples by staining. Microarray analysis found two genes involved in migration and progression; CXCR4 and ADAMTS1 were studied. ERG binds to these genes. ERG aberrant expression leads to CXCR4 over-expression and to a lesser extent ADAMTS4 expression. This model provides a mechanism to further study these pathways and link these genetic rearrangements with biological events.

Presented by B. S. Carver at the American Society of Clinical Oncology (ASCO) - 2008 Genitourinary Cancers Symposium - A Multidisciplinary Approach - February 14-16, 2008 San Francisco, California, USA

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS Professor & Chairman Department of Urology University of California, Davis, School of Medicine Sacramento, CA

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