733 DIFFERENTIAL EXPRESSION OF PROSTAGLANDIN RECEPTORS IN PROSTATE CANCER: A NOVEL THERAPEUTIC TARGET?

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011733 DIFFERENTIAL EXPRESSION OF PROSTAGLANDIN RECEPTORS IN PROSTATE CANCER: A NOVEL THERAPEUTIC TARGET? Hosea Huang, Ping Shu, Thomas Murphy, Seena Aisner, and Mark Jordan Hosea HuangHosea Huang Newark, NJ More articles by this author , Ping ShuPing Shu Newark, NJ More articles by this author , Thomas MurphyThomas Murphy Newark, NJ More articles by this author , Seena AisnerSeena Aisner Newark, NJ More articles by this author , and Mark JordanMark Jordan Newark, NJ More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1702AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostaglandin E2 (PGE2) exerts its functions via the prostanoid receptors, EPR1-4. Since PGE2 has been implicated in prostate cancer (CaP) tumorigenesis, we hypothesized that abnormal EP receptor expression may contribute to CaP growth. METHODS Twenty-six (26) consecutive radical prostatectomy specimens were assessed. Areas of histologically proven CaP and benign tissue (NP) were compared by immunohistochemistry (IHC) and Western blot for expression of EP1, EP2, EP3, and EP4. As a corollary, EPR expression in one normal (PZ-HPV7) and four CaP cell lines (CA-HPV10, LnCaP, PC3 and Du145) were compared by RT-PCR and Western blot in vitro. CaP and NP cell growth was also assessed in vitro after selective siRNA EPR knockdown. All studies were approved by the local IRB and 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, CaP tissue overexpressed EP4 and EP2 in 85% (22/26) and 69% (18/26) of clinical samples, respectively (p<0.05); in contrast, EP3 expression was reduced in all (26/26) clinical samples (Figure 1). EP1 showed no specific differential expression pattern. These findings were corroborated by higher EP4 but lower EP3 levels in all 4 CaP cell lines (CA-HPV10, LNCaP, PC3 and Du145) when compared to a NP cell line (PZ-HPV7) (Figure 2). EP2 and EP4 siRNA knockdown also suppressed (p<0.05) the in vitro growth of CaP cell lines. CONCLUSIONS CaP is associated with EP4 and EP2 over-expression and reduced EP3 expression. The functional significance of EP2/EP4 over-expression was confirmed by the inhibition of CaP cell growth after siRNA knockdown. These data show that abnormal expression of EP2 and EP4 may play a role in CaP growth. The role of EP3 is being further explored in our laboratory. Targeting specific EPR may thus represent a novel therapeutic approach for CaP. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e294-e295 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hosea Huang Newark, NJ More articles by this author Ping Shu Newark, NJ More articles by this author Thomas Murphy Newark, NJ More articles by this author Seena Aisner Newark, NJ More articles by this author Mark Jordan Newark, NJ More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...