Histone H3K27 Tri-Methylation Mediates Metastatic Phenotype in Breast Cancer Cells

Document Type


Degree Name

Master of Science (MS)


Biological and Environmental Sciences

Date of Award

Spring 2015


Although metastasis causes over 90% of breast cancer mortalities, the mechanisms that mediate the transition of breast cancer cells from the epithelial to mesenchymal phenotype (EMT) is still unclear. Changes in histone modifying enzymes is associated with EMT induction. Since histone protein kinase C (PKC) plays a role in mediating histone modifying enzymes, we hypothesized that protein kinase C plays a role in breast cancer metastasis by decreasing H3K27 tri-methylation (H3K27me3), therefore causing H3K27me3 reorganization. Histone tri-methylation was decreased in non-metastatic MCF-7 cells using phorbol 12-myristate 13-acetate (PMA) and cell H3K27me3 levels, morphology, migration, invasion, and EMT gene profile were assessed. In wound healing assays, PMA treatment significantly increased cell migration at 24 hours [2.5 fold, p = < 0.0001] and invasion at 72 hours 58 fold, [p = < 0.0001]. In addition to PMA inducing the EMT phenotype by 2 hours, PMA significantly increased the expression of EMT gene markers Snail and Twist [4.1 fold, p = 0.0001] and Vimentin [5 fold, p = < 0.0001]. Inhibition of PKC by Bisindolyleimide I (BIM1) resulted in MCF-7 cells migrating significantly slower in comparison to untreated cells. Our results suggest that PKC may mediate breast cancer metastasis by regulating the organization of H3K27me3.


Venugopalan Cheriyath

Subject Categories

Biology | Life Sciences