ERG-Mediated Repression of HPGD in Prostate Tumorigenesis.
Ahmed Mohamed, Taduru Sreenath, Shyh-Han Tan, Chen Sun, Syed Shaheduzzaman, Ying Hu, Gyorgy Petrovics, Yongmei Chen, David McLeod, Albert Dobi, Shiv Srivastava, Isabell Sesterhenn. Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Rockville, MD; Armed Forces Institute of Pathology, Washington, DC; Walter Reed Army Medical Center, Washington, DC
Background: Activation of the ETS Related Gene (ERG) was originally identified in subsets of Ewing sarcomas, myeloid leukemias and, recently, in the majority of prostate cancers. Recent studies have indicated that 15−hydroxy−prostaglandin dehydrogenase (HPGD), a tumor suppressor, is down regulated in a majority of lung, colon, breast, and bladder cancers. However, the regulation of HPGD within the biological context of ERG expressing prostate tumors remain to be defined. The objective of this study was to evaluate effects of ERG on the prostaglandin pathway in prostate cancer.
Design: Correlation between HPGD and ERG expression was evaluated at the mRNA and protein levels in prostate cancer specimens. Small interference RNA against human ERG and HPGD were used to knock−down ERG and HPGD expressions. Functional consequences of ERG and HPGD knock−down were assessed in ERG expressing VCaP cells harboring TMPRSS2-ERG fusions.
Results: Comparison of HPGD expression in ERG positive and negative prostate tumors revealed a trend towards decreased HPGD expression. We found robust overexpression of HPGD in response to ERG knock−down in VCaP prostate tumor cells. Chromatin immunoprecipitation experiments revealed the recruitment of ERG protein to the HPGD core promoter.
Conclusions: Expression of ERG in prostate tumorigenesis may disrupt suggested tumor suppressor functions of HPGD.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 101, Monday Afternoon