Expression and epigenetic silencing of ECRG4gene in breast cancer

Abstract

11046 Previous whole-genome expression array studies in our laboratory had shown the expression of ECRG4 (esophageal cancer related gene 4) was significantly down-regulated in primary breast cancer. The present study was undertaken to investigate the expression and epigenetic regulation ofECRG4in human breast cancer cell lines and primary carcinomas. Here we showed that the expression ofECRG4, as measured by quantitative reverse transcription-PCR, was noticeably increased in 3 methylated breast cancer cell lines (MDA-MB-435, Bcap-37, MCF-7), after treated with 5-aza-2’-deoxycytidine - a demethylation agent. Analysis from 16 paired tissue samples revealed expression of ECRG4 was significantly reverse-correlated with methylation (Spearman correlation coefficient r=-0.419, P=0.017). Analysis of 67 additional samples showed that the ECRG4 CpGs island was in high methylation level in 59.7% of cancer tissues compared with 14.9% in tumor adjacent tissues,with an odds ratio of 3.393 (95% CI, 1.912–6.021,P=8.39E-8). And patients with high methylation level had a higher tumor grade. 90% samples were high methylation levels in grade III vs. 50% in grade I-II (95% CI, 1.063–76.213, P=0.033). In conclusion, the inactivation of ECRG4 gene by hypermethylation appears to be a frequent molecular event in development of primary breast cancer and may be involved in the carcinogenesis of this cancer. No significant financial relationships to disclose.