Abstract 5384: Hrev107 enhances prostaglandin D2 synthase-mediated cancer cells suppression in the testis.

Abstract

Abstract Hrev107, also called HRASLS3 or PLA2G16, is a member of the HREV107 type II tumor suppressor gene family which includes HREV107, Retinoid-inducible gene 1 (RIG1), and HRASLS. The protein in this family contains an NC domain, with unknown function at the N-terminus, and a hydrophobic membrane-anchoring domain at the C-terminus. HREV107 has shown that expressed at high levels in differentiated tissues of post-meiotic testicular germ cells but not in human testicular germ cell tumors. Prostaglandin D2 (PGD2) has shown that can induce SOX-9 nuclear translocation and subsequent Sertoli cell differentiation. In addition, expression of the Prostaglandin D2 synthase (PTGDS) has been detected in the cellular lineage. This gives rise to the Sertoli cells, and the Sertoli cells appear to express the PTGDS only during the VI-VIII stages of the spermatogenic cycle after spermiation. These results suggested that PGD2 may play an important role in the testis differentiation. Our previous result showed that RIG1 (as RIG1 is expressed in the human species only) can interact with PTGDS. We further examined the effect of mouse Hrev107 on the growth of mouse testicular cells. When Hrev107 was expressed in TM3 or TM4 mouse testicular cancer cells, the cell migration and invasion were inhibited. Further, we found PTGDS was co-localized with Hrev107 in TM4 testis cells. In Hrev107-expressing NT2/D1 cells, elevated levels of PGD2, cAMP, and SRY-related high-mobility group box 9 (SOX9) were observed. This result indicated that Hrev107 can enhance PTGDS activity. Silencing of PTGDS expression significantly decreased h-REV107-mediated cAMP and PGD2 production. Furthermore, silencing of PTGDS or SOX9 alleviated Hrev107-mediated suppression of migration and invasion. These results suggest that Hrev107 will suppress cell migration/invasion through the PGD2 signaling pathway. In conclusion, Hrev107 can interact with PTGDS to enhance its function and to further suppress NT2/D1 cell migration and invasion. Citation Format: Fu-Ming Tsai, Chang-Chieh Wu, Rong-Yaun Shyu, Shun-Yuan Jiang. Hrev107 enhances prostaglandin D2 synthase-mediated cancer cells suppression in the testis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5384. doi:10.1158/1538-7445.AM2013-5384