Abstract 2043: BORIS directly regulates in vivo expression of the cancer testis antigen, testes-specific protease 50 (TSP50)

BORIS (Brother of the Regulator of Imprinted Sites), also known as CTCFL, is a paralogous gene of that encoding the versatile chromatin factor CTCF. While BORIS was initially described as a testis-specific gene, recent reports showed that it is also expressed in various tumors and cancer cell lines at the transcriptional and protein levels indicating that BORIS encodes a cancer testis antigen (CTA). Interestingly, several studies have shown that BORIS regulates the expression of other CTAs including MAGE-A1 and NY-ESO-1. Gene expression profiling of testes derived from BORIS knockout and wild type mice suggested that BORIS regulates the expression of another gene encoding a CTA, testes-specific protease 50 (TSP50), also known as PRSS50. To examine this suggestion, we first performed electrophoretic mobility shift assays (EMSA) and found that the mouse TSP50 promoter region contains two BORIS binding sites. Occupancy of these sites by BORIS was confirmed by ChIP analyses of testicular chromatin. Computer analyses of the human TSP50 promoter revealed extensive homology with the mouse TSP50 promoter within BORIS binding sites. We confirmed BORIS binding to those sites by EMSA. Moreover, ChIP analyses of human cancer cell lines expressing TSP50 also showed that BORIS was bound to the promoter. Luciferase reporter assays demonstrated the importance of BORIS for the regulation of TSP50 promoter. Finally, we found that BORIS-induced expression of TSP50 is epigenetically regulated. These findings represent the first demonstration that the CTA, BORIS, itself regulates the expression of other CTAs in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2043. doi:10.1158/1538-7445.AM2011-2043