Abstract 345: Prostaglandin receptors differentially regulate prostate cancer growth: A novel treatment target

Abstract

Abstract INTRODUCTION AND OBJECTIVE: Prostaglandin E2 (PGE2) acts through a series of distinct prostanoid receptors, EPR 1-4. Since PGE2 is implicated in prostate cancer (CaP) tumorigenesis and metastasis, we hypothesized that EP receptor expression may influence CaP growth. METHODS: 27 consecutive radical prostatectomy specimens were assessed by immunohistochemistry (IHC) for EPR expression and compared with normal human prostate epithelium (NP) from the same specimen as control. As a corollary, the expression of EP receptors in both normal (PrEC, PWR1E and PZ-HPV7) and CaP cells (LNCaP, PC3 and CA-HPV10) were assessed by RT-PCR and Western blot. The functional significance of EPR was assessed by growth of malignant and benign cell lines in vitro after siRNA EPR knockdown. All studies were approved by the local institutional review board (IRB) and all in vitro experiments performed a minimum of 3 times. RESULTS: EP1, EP2, EP3 and EP4 receptors were detected by IHC in all NP clinical specimens. Compared with NP, EP4 and EP2 were over-expressed in 74% (20/27) and 63% (17/27) of CaP specimens, respectively; in contrast, EP3 expression was reduced in 93% (25/27) clinical samples (Figure). EP1 showed no specific differential expression pattern. Western blot showed increased EP4 but reduced EP3 in CaP lines (CA-HPV10, LNCaP and PC3) compared with NP lines; EP2 and EP4 knockdown significantly suppressed whereas EP3 knockdown stimulated in vitro growth of CA-HPV10 vs PZ-HPV7 cells. Expression of Runx 2 and MMP9, (known to contribute to CaP metastatic potential) was also reduced after EP2 and EP4 knockdown in CaP cells. CONCLUSION: We observed EP4 and EP2 over-expression and reduced EP3 expression in 27 consecutive resected CaP specimens and in 6 representative cell lines. These observations were corroborated by the effects of EP4, EP2 and EP3 knockdown on tumor cell growth in vitro. These data suggest that EP receptor subtypes may regulate CaP growth which may represent a novel therapeutic approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 345.