Abstract 4007: Different expression of <i>AHCYL1</i> affecting ovarian carcinogenesis between chickens and women
Authors: Hee Seung Kim, Wooyoung Jeong, Young Beom Kim, Min A Kim, Noh Hyun Park, Fuller W Bazer, Jae Yong Han, Gwonhwa Song, Yong Sang Song
Journal: Cancer Research (2012)

Abstract S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) is the evolutionarily conserved and ubiquitously expressed enzyme that catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine, a byproduct of the S-adenosyl-L-homomethionine-dependent methyltransferase reaction, into adenosine and homocysteine. It acts like an inositol 1,4,5-triphosphate receptor (IP3R)-binding protein (termed IP3R-binding protein released with inositol 1,4,5-triphosphate, or IRBIT) by competitively inhibiting the interaction of IP3 with IP3R. As a result, AHCYL1 regulates IP3-induced Ca2+ signaling which plays crucial roles in numerous cellular processes including gene expression and cell death. However, it is still poorly understood about the expression of AHCYL1 affecting clinical outcomes in epithelial ovarian cancer (EOC). In the current study, we identified AHCYL1 affecting ovarian carcinogenesis in chickens, the most relevant model, and investigated its prognostic value in patients with EOC. In 136 chickens, ovarian cancer was detected in 10 (7.4%). We compared the expression and localization of AHCYL1 mRNA and protein between normal and cancerous ovaries of chickens using reverse transcription polymerase chain reaction, in situ hybridization and immunohistochemistry, and AHCYL1 activation was detected in chicken and human ovarian cancer cell lines (OVCAR-3, SKOV-3 and PA-1) using immunofluorescence microscopy. Thereafter, we examined the prognostic value of AHCYL1 expression in patients with EOC by multivariate linear logistic regression and Cox’ proportional hazard. As a result, AHCYL1 mRNA was induced in cancerous, but not normal ovaries of chickens (p&amp;lt;0.01), and it was abundant only in the glandular epithelium of cancerous ovaries of chickens. AHCYL1 protein was localized predominantly to the nucleus of glandular epithelium in cancerous ovaries of chickens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 14 (12.8%), 41 (37.6%) and 54 (49.6%) patients showed weak, moderate and strong expression of AHCYL1 protein, respectively. However, intermediate or high expression of AHCYL1 protein was a favorable factor for overall response (adjusted OR, 7.23; 95% CI, 1.36-38.39), and for progression-free survival (PFS; adjusted HR, 0.20; 95% CI, 0.07-0.55). Conclusively, AHCYL1 may be associated with ovarian carcinogenesis in both chickens and human. In contrast to AHCYL1 expression associated with ovarian carcinogenesis in chickens, it is expected to play a role as tumor suppressor gene in human EOC because a higher expression of AHYCL1 was related with better OR and PFS. Finally, the functional role of AHCYL1 showing different expression in ovarian carcinogenesis between chickens and women should be further investigated by more relevant studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4007. doi:1538-7445.AM2012-4007