Glucocorticoid induced expression of connective tissue growth factor contributes to lactogenic differentiation of mouse mammary epithelial cells

The response of mammary epithelial cells to basement membrane and stroma induced signals contributes to the degree of differentiation in this tissue. The studies reported here indicate that connective tissue growth factor (CTGF) is highly elevated during lactogenic differentiation of the HCI 1 mouse mammary epithelial cell line. In addition, CTGF is expressed in the mouse mammary gland during pregnancy and lactation and it is expressed in primary mammary epithelial cell cultures established from pregnant mice. In HCI 1 cells CTGF is transcriptionally regulated by dexamethasone, but not by estrogen or progesterone, and CTGF expression is not dependent on TGF beta. CTGF contributes to and is required for lactogenic differentiation of HCI 1 cells, as demonstrated by increased differentiation following expression of plasmid-encoded CTGF and decreased differentiation following depletion of endogenous CTGF with siRNA. Moreover, HCI 1 mouse mammary epithelial cells infected with an adenoviral vector encoding CTGF exhibit increased lactogenic differentiation. Plasmid vector-induced elevation of CTGF levels also increased the level of beta 1 integrin in HCI 1 cells. Because the production of stromal factors is an important component of differentiation in mammary epithelial cells, the regulation of CTGF by glucocorticoids may play a critical role in this aspect of the control of differentiation. The studies reported here provide important information on the role of CTGF in mammary epithelial cell differentiation.