390 THE JOURNAL OF UROLOGY ® Vol. 179, No. 4, Supplement, Monday, May 19, 2008 Source of Funding: GENAU-Project / Austria. 1133 METASTASIS-ASSOCIATED PROTEIN 1 AS A POTENTIAL BIOMARKER AND TARGET FOR THE MANAGEMENT OF PROSTATE CANCER BONE METASTASES Li Kai, Jun Wang, Yeon T Chung, Jennifer Jerrett, William B Laskin, Chiang C Huang, Robert S Satcher, Anait S Levenson*. Chicago, IL, and Houston, TX. INTRODUCTION AND OBJECTIVE: Skeletal metastases are most common in prostate cancer (PCa) with no effective therapies. We have previously generated in vitro model of cancer/bone interaction to metastasis-associated protein 1 (MTA1) to be overexpressed in PCa cells. MTA1 is a transcription factor associated with chromatin remodeling and gene repression, its expression is connected with aggressive the prognostic and therapeutic value of MTA1 in the development and progression of PCa bone metastases. METHODS: In vitro cell co-culture, FACS, cDNA microarrays, western blotting, real time RT-PCR, RNAi technology, migration and invasion assays, in vivo intracardiac mouse model, tissue microarrays (TMAs) & immunohistochemistry, statistical analysis. RESULTS: Microarray analysis of co-cultured PC3 cells showed MTA1 overexpression compared to PC3 alone. To assess the role of MTA1 in bone metastases, we created PC3 cells with cells revealed that MTA1 silencing decreased VEGF and increased MMP2 levels in the conditioned media of the cells and inhibited in vitro invasion and migration. In vivo experiments are in progress to evaluate the functional involvement of MTA1 in the progression of PCa bone metastases. To determine whether MTA1 is a useful biomarker for aggressive tumors that develop bone metastases, we evaluated MTA1 protein expression in normal prostate, adenocarcinoma and bone metastatic lesions using TMAs. MTA1 was not expressed in normal prostate but was present in all tissues of adenocarcinoma and bone it was in both cell nucleus and cytoplasm whereas in bone lesions it was exclusively in the nucleus. Further analysis indicated that in high grade PCa (Gleason >7) it was mostly in the nucleus while in low grade PCa correlation between MTA1 intensity/frequency in nucleus/cytoplasm ratio and PSA (p=0.0001): tumors from patients with high PSA (>11 ng/ ng/ml), whose tumors showed mainly cytoplasmic staining. CONCLUSIONS: MTA1 holds promise as a biomarker for aggressive PCa and a molecular target for the development of new therapeutics to combat bone metastases. Source of Funding: None 1134 VEGF TREATMENT OF MICROVASCULAR ENDOTHELIAL CELLS INDUCES BCL-2 EXPRESSION AND MULTIPLE SIGNALING FACTORS Yoshihisa Sakai*, Steve Goodison, Wengang Cao, Kazunori Namiki, Stacy Porvasnik, Charles J Rosser. Gainesville, FL. INTRODUCTION AND OBJECTIVE: The tumor microenvironment plays a major role in establishing and maintaining tumoral angiogenesis. Previously we demonstrated that Bcl-2 expressing prostatic tumors, are not only more tumorigenic but are more angiogenic. Increased rates of angiogenesis could be due to these cancer cells Vascular Endothelial Growth Factor (VEGF). METHODS: HMVEC treated with VEGF, conditioned media from Bcl-2 expressing human prostate cancer cells, conditioned media from non-Bcl-2 expressing human prostate cancer cells and unconditioned media were subjected to in vitro proliferation assay, qPCR, mRNA stability assay, Western blot analysis and microarray analysis. RESULTS: We show that VEGF stimulation of human endothelial cells induces Bcl-2 Bcl-2, and protects these endothelial cells from apoptosis. Furthermore, exposure of these human endothelial cells to conditioned media from Bcl-2 expressing cancer cells also resulted in up regulation of Bcl-2 expression. Indeed the importance of Bcl-2 expression is evident by the fact that at least four distinct pathways (i.e., mTOR, PI3K, PKC, and ERK) contribute to Bcl-2 expression in endothelial cells. Microarray analysis of endothelial cells subjected to culture media from Bcl-2 expressing human prostate cancer cells triggered a transcriptional program of genes involved in cellular metabolism, cell recognition and communication, Bcl-2 conditioned media compared to controls (media from PC-3-Neo and DMEM media) and were noted to interact with other key molecules associated with tumor survival and growth. CONCLUSIONS: Collectively, these data suggest that exposure of human endothelial cells to the extracellular milieu of Bcl-2 expressing tumor stimulates Bcl-2 expression in endothelial cells leading to increase proliferation, resistance to apoptosis and a unique molecular association between Bcl-2 expression and enhanced angiogenesis and suggest strategies designed to overcome the survival advantaged afforded to endothelial cells by Bcl-2 might aid in enhancing treatment response. Source of Funding: None 1135 A NOVEL HIGH THROUGHPUT SCREEN IDENTIFIES POTENT SENESCENCE-INDUCING ACTIVITY OF DIAZIQUONE (AZQ) IN PROSTATE CANCER CELLS Jonathan A Ewald, Timo Laurila, Nima Almassi, Joshua A Dosetelle, David F Jarrard*. Madison, WI. INTRODUCTION AND OBJECTIVE: Cellular senescence is a terminal response in normal and transformed cells to multiple factors,