A mammary epithelial cell line is transiently stimulated towards milk lipid synthesis by lactogenic treatments

Abstract

A subcloned mouse mammary epithelial cell line (COMMA-D/MME) was cultured on Engelbreth-Holm-Swarm (EHS) tumor cell matrix with lactogenic hormones (insulin, cortisol, prolactin) to stimulate differentiation and challenged with growth factors to interpret the relationship between the signals for growth and differentiation. After 21 days of pretreatment to promote differentiation, cells were capable of growth, but were always less responsive than cells that did not receive lactogenic pretreatment. Although the cells failed to express β-casein mRNA, droplets of neutral lipids were present in the cell cytoplasm regardless of treatment. Lactogenic hormones induced the appearance of larger droplets that occured in intracytoplasmic lumens and lipid synthesis rates were initially increased. However, the glycerol incorporation pattern of these lipids only reached 53% of the changes expected for lactating tissue. Furthermore, because secretion of the lipid was inhibited, the accumulation eventually inhibited synthetic capacity. The cellular expression of acetyl Co-A carboxylase message was increased by growth, but not by lactogenic treatments. It is concluded that the COMMA-D/MME are capable of partial and transient differentiation to synthesize milk lipids, but are inhibited by the accumulation of material due to the inability to secrete.