One DNA Methylation Regulates CHIP Gene Expression of Human Breast Cancer and Predicts Recurrence

Abstract

Background/aim: Carboxyl terminus of Hsc70-interacting protein (CHIP) is a ubiquitin ligase that induces ubiquitination and degradation of its target proteins including oncoproteins. We reported that its down-regulation is associated with tumor progression and metastasis of breast cancer. However, the mechanism through which CHIP gene affects cancer cells is unclear.

Materials and methods: We extracted RNA from 45 primary breast cancer samples and compared CHIP mRNA expression profiles, promoter DNA methylation status, and clinicopathological information.

Results: CHIP mRNA expression was significantly correlated with the tumor progression status. In several samples, a pinpoint CpG methylation in the CHIP gene promoter region was significantly correlated with CHIP mRNA expression. When this specific CpG was methylated in estrogen receptor (ER)-positive cases, a significant difference in 5-year recurrence was not found compared with ER-negative cases.

Conclusion: CpG methylation contributes to the long-term prognosis of ER-positive breast cancer.

Keywords: Breast cancer recurrence; CHIP; DNA methylation; ER.