correlated with expression of N-cadherin after treatment with met-formin. Moreover, we also found that metformin inhibited expression ofTWIST-1, a transcriptional activator of N-cadherin. Similar findingswere observed by confocal microscopy. PC3 prostate cancer cells withstable over-expression of TWIST-1 became resistant to metformin-mediated inhibition.

CONCLUSIONS: We demonstrate that Metformin’s anti-cancertherapeutic effect may be mediated through repression of the TWIST/N-cadherin signaling pathway.

Source of Funding: None

804OVEREXPRESSION OF THE CANCER/TESTIS ANTIGENJARID1B, CONTRIBUTES TO THE SURVIVAL OF PROSTATECANCER CELLS UNDER ANDROGEN DEPLETED CONDITIONS

Takumi Shiraishi*, Naoki Terada, Steven Mooney, Yu Zeng,Sayuri Takahashi, Jun Luo, Robert Getzenberg, Prakash Kulkarni,Baltimore, MD

INTRODUCTION AND OBJECTIVES: Many studies haveshown that androgen receptor (AR) signaling is reactivated in castra-tion-resistant prostate cancer (CRPC). However, it remains unclearhow prostate cancer (PCa) cells can survive under androgen-depletedcondition until progression to CRPC in which AR signaling is reacti-vated. JARID1B belongs to the Cancer/Testis Antigen group of proteinsthat are typically restricted to the testis but are aberrantly expressed inseveral types of cancer. JARID1B is also member of the highly con-served family of jumonji/ARID1 (JARID1) histone 3 K4 (H3K4) dem-ethylases which are involved in development, cancer, and in maintain-ing the pluripotency of stem cells. The aim of this study was toinvestigate the contribution of JARID1B to the survival of PCa cellsunder androgen-depleted conditions.

METHODS: JARID1B expression in PCa samples was deter-mined by real-time PCR. Cell growth, colony formation assay and cellcycle were examined in LNCaP and LNCaP-J1B (JARID1B over-expressing LNCaP) cells. The effect of JARID1B on AR transcriptionalactivity was assessed in PC3 cells.

RESULTS: Among chromatin modifying enzymes, JARID1Bwas identified as the one that was the most induced in LNCaP cells inresponse to androgen depletion using a focused PCR array. JARID1Bwas up-regulated both in localized and metastatic PCa samples com-pared to normal prostate. The induction of JARID1B followed by thereduction of tri-methyl (3me) H3K4 levels was observed in LNCaP cellsafter androgen depletion and the reduction of 3meH3K4 levels wasabolished by the knockdown of JARID1B. Over-expression of JARID1Breduced cell proliferation rate in normal medium, but no change wasobserved in cell growth under androgen-depleted medium. After pre-culturing cells with androgen-depleted medium for 7 days, LNCaP-J1Bcells exhibited an increased colony formation rate compared to controlcells when they were returned to normal medium. Increased proportionof cells at G1 phase by androgen-depletion was reduced whenJARID1B was over-expressed. Furthermore, JARID1B showed a li-gand-independent increase of AR transcriptional activity.

CONCLUSIONS: Taken together, these results suggest thatJARID1B might be associated with the survival after androgen-deple-tion through the control of cell cycle and AR transcriptional activity.Thus, JARID1B may represent a potential therapeutic target to inhibitthe development of CRPC.

Source of Funding: The David Koch Foundation to PK.

Sexual Function/Dysfunction/Andrology: BasicResearch (I)

Moderated Poster Session 31

Monday, May 6, 2013 8:00 AM-10:00 AM

805CHRONYC ADMINISTRATION OF SILDENAFIL IMPROVESERECTILE FUNCTION IN A RAT MODEL OF CHRONIC RENALFAILURE

Mustafa Faruk Usta*, Arif Kol, Nilgun Gurbuz, Asli Baykal, Antalya,Turkey

INTRODUCTION AND OBJECTIVES: The relationship be-tween Erectile Dysfunction (ED) and Chronic Renal Failure (CRF) hasbeen reported in several studies. In the present study, we investigatewhether the chronic use of sildenafil could enhance the erectile cap-asity in CRF-induced rats. Additionally, we evaluated the impact of thattreatment option on some molecules, which have been accepted ascrucial factors playing important roles in erectile physiology and CRFrelated ED as well.

METHODS: Three groups of animals were utilized: (1) age-matched control rats, (2)CRF induced rats, (3)CRF-induced ratstreated with chronic administration of sildenafil (5mg/kg p.o.; for 3months). At three months, all animals underwent cavernosal nevrestimulation (CNS) to assess erectile function. Penile tissue AdvancedGlycation End Products (AGEÆs/5-HMF), Malondialdehyde (MDA),cGMP (ELISA), iNOS and nNOS (Western Blot) analysaes were per-formed in all groups of rats.

RESULTS: CRF-induced rats had a significant decrease inerectile function as determined by the peak intracavernosal pressure(ICP) and total ICP (area under the curve; AUC) after CNS whencompared to control rats (p�0.05). The increase in both ICP and AUCof CRF-induced rats treated with sildenafil (Group-3) was significantlygreater then CRF-induced rats (Group-2). Additionally, sildenafil treat-ment decreased AGE, MDA and iNOS levels, while it preserved nNOSand cGMP contents in CRP-induced penile tissue.

CONCLUSIONS: Decreased AGE, MDA, YNOS and increasednNOS, cGMP levels at the sildenafil treated group increased bot ICPand total ICP to CNS in the CRF-induced rat, which was similar to theresponse observed in control rats. These results may suggested thetherapeutic effect of chronic sildenafil administration on erectile func-tion in CRF-induced rats.

Source of Funding: None

806INTRATUNICAL INJECTION OF HUMAN ADIPOSETISSUE-DERIVED STEM CELLS PREVENTS FIBROSIS AND ISASSOCIATED WITH IMPROVED ERECTILE FUNCTION IN A RATMODEL OF PEYRONIE’S DISEASE.

Fabio Castiglione*, Petter Hedlund, Milan, Italy; Frank van der Aa,Leuven, Belgium; Trinity J. Bivalacqua, Baltimore, MD;Maarten Albersen, Leuven, Belgium

INTRODUCTION AND OBJECTIVES: Peyronie’s disease (PD)is a connective tissue disorder of the tunica albuginea (TA). Currently,no gold standard has been developed for the treatment of the diseasein it’s active phase. Objective: To test the effects of local injection ofadipose tissue-derived stem cells (ADSC) in the active phase of a ratmodel of PD on subsequent development of fibrosis and elastosis ofthe TA and underlying erectile tissue.

METHODS: Twenty-seven male 12 weeks old spraque-dawleyrats were divided in three equal groups and underwent injection ofeither vehicle (sham), 50 �g TGF-�1 in 50 �L vehicle (PD andPD�ADSC group) in the dorsal aspect of the tunica albuginea. Thesham and PD groups were treated one day after TGF-�1 injection with

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