DNA Methylation of the Keratin 18 Gene Regulates Brain Metastasis of Triple Negative Breast Cancer

Breast cancer patients with brain metastasis have a poor prognosis and current chemotherapeutic agents are largely ineffective, which led us to seek new chemotherapeutic agents for the treatment. Our preliminary results showed the hypomethylating agent azacitidine (abbreviated as AZA) is effective in treating brain metastasis breast cancer using in vitro cell and in vivo preclinical mouse models. In the present study, we explored the molecular mechanism of action of AZA for this treatment. Keratin 18 is a member of the cytokeratin family proteins (epithelial marker). We observed that the keratin 18 gene is present in both parental regular MDA‐MB‐231 triple negative breast cancer cells (“231”) and their brain metastasized counterpart cells (“231Br”). However, mRNA and protein levels of keratin 18 are significantly decreased in 231Br cells compared to 231 cells.