Abstract 1070: Epigenetic silencing of galectin-12 in colorectal cancer

Abstract

Abstract Aim/Background: Galectins constitute a family of ß-galactoside binding proteins some of them known to be involved in colorectal tumorigenesis. Our previous work suggests that sodium butyrate can induce galectin-12 expression in CRC cell lines. How this might be exerted is largely unexplored. In the present study we examined the potential epigenetic regulation of galectin-12 expression in colorectal cancer cell lines and primary tumors. Material and Methods: For DNA-methylation analysis 4 microsatellite unstable (MSI) and 5 microsatellite stable (MSS) human CRC cell lines were treated with 5-Aza-2`deoxycytidine (5-Aza-dC) for 72h. Changes in galectin-12 expression were evaluated by RT-PCR analysis. Galectin-12 promoter methylation was determined by bisulfite treatment and genomic DNA sequencing of single clones in the CRC cell line SW707 as well as in FFPE specimens from 10 primary colorectal tumors (MSI: n = 5; MSS: n = 5). Results: Treatment with 5-Aza-dC led to de novo expression of galectin-12 transcript in 4/9 (44%) of colorectal cancer cell lines. We identified a CpG island in the galectin-12 promoter region that was found to be hypomethylated upon 5-Aza-dC treatment in SW707 cells and to be associated with concomitant de novo galectin-12 mRNA expression. When primary tissues were examined we observed galectin-12 promoter hypomethylation in healthy colon mucosa but significant hypermethylation of this promoter region in corresponding tumor tissue. Conclusions: This study for the first time shows that galectin-12 promoter methylation represses galectin-12 expression in colorectal tumor cells independent of their MSI status. In CRC cell lines this effect can be reversed by butyrate but in human colon primary tumors might be refractory to these effects of butyrate. Re-expression of galectin-12 may be a potential therapeutic strategy to constrain colorectal tumor growth. Citation Format: Eva-Maria Katzenmaier, Johannes Gebert, Matthias Kloor, Jürgen Kopitz. Epigenetic silencing of galectin-12 in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1070. doi:10.1158/1538-7445.AM2015-1070