Inhibiting SETD7 methyl ‐transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary epithelial cells

SETD7 (SET7/9, KMT7) is a lysine methyltransferase that regulates several pathways. In mammary epithelial cells (HC11 and EpH4), inhibiting SETD7 catalytic activity with the compound (R)-PFI2 increased cell proliferation, altered expression of E-cadherin, beta-catenin, lactoferrin, insulin-like growth factor binding protein 5, and beta-casein, and disrupted the lipid profile. These findings indicate that inhibiting SETD7 activity impairs mammary epithelial and lactogenic differentiation. SETD7 (SET7/9, KMT7) is a lysine methyltransferase that targets master regulators of cell proliferation and differentiation. Here, the impact of inhibiting SETD7 catalytic activity on mammary epithelial cell differentiation was studied by focusing on genes associated with epithelial differentiation, lactogenesis, and lipid metabolism in HC11 and EpH4 cell lines.Setd7 mRNA and protein levels were induced upon lactogenic differentiation in both cell lines. Inhibition of SETD7 activity by the compound (R)-PFI-2 increased cell proliferation and downregulated E-cadherin, beta-catenin, lactoferrin, insulin-like growth factor binding protein 5, and beta-casein levels. In addition, inhibition of SETD7 activity affected the lipid profile and altered the mRNA expression of the phospholipid biosynthesis-related genes choline phosphotransferase 1, and ethanolamine-phosphate cytidylyltransferase. Altogether, the results suggest that inhibiting SETD7 catalytic activity impairs mammary epithelial and lactog...
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Article Source Type: research