Abstract 4018: DNA methylation controls CHST11 gene expression in breast cancer

Abstract

Listen

Translate article

Abstract Introduction: We have previously demonstrated that chondroitin sulfates (CS) play a crucial role in metastatic potential of breast cancer cells. We have shown that the expression level of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with CS-A expression and aggressiveness of human breast cancer cells. The current study was mainly performed to determine whether the expression of CHST11 gene in breast cancer cells is controlled by DNA methylation. Methods: Quantitative real-time PCR was used to detect the expression of CHST11 in human breast cancer cell lines. MCF7 cells were treated with 5-aza-2′-deoxycytidine (5AzadC) for DNA demethylation and expression analysis. Methylation in MCF7, MDA-MB-231 cells and patient breast cancer specimens was analyzed using bisulfite genomic sequencing (BGS). Reduced representation bisulfite sequencing (RRBS) was performed in the CpG island of CHST11 with a minimum coverage of 10. Digital gene expression was used to estimate the number of transcribed copies of the CHST11 gene from the second-generation mRNA-sequencing data. Results: Treatment of MCF7 cells with 5-AzadC increased the expression of CHST11 and its product CS-A in a dose-dependent manner. We observed very low levels of DNA methylation in a CpG island of CHST11 in estrogen receptor-negative basal-like cell lines MDA-MB-231, MDA-MB-468, and BT-20, but very high levels in the same region in estrogen receptor-positive luminal MCF7, ZR-75-1, and T47-D cells. We found that the CpG island can also be hypomethylated in triple negative (negative for estrogen and progesterone receptors and Her2/neu) patient breast cancer tissues. Conclusions: The data suggest that DNA hypomethylation significantly contributes to CHST11 and surface CS-A expression in aggressive breast cancer cells. The data suggest that therapeutic use of DNA demethylating agents may promote more aggressive forms of breast cancer. 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 4018. doi:1538-7445.AM2012-4018