Cell-extracellular matrix interactions and EGF are important regulators ofthe basal mammary epithelial cell phenotype

The mammary epithelium is composed of a luminal epithelium and a basal laye r containing myoepithelial cells and undifferentiated precursors. Basal cel ls express specific protein markers, such as keratin 14 (K14) and P-cadheri n, To study the factors that regulate the basal mammary epithelial cell phe notype, we have established two clonal derivatives of the mouse HC11 cell l ine, BC20 and BC44, expressing high levels of K14 and P-cadherin, Unlike th e parental HC11 cells, these basal cells did not produce beta-casein in res ponse to lactogenic hormone treatment; however their phenotype appeared to be plastic. Cultured in EGF-free medium, they exhibited enhanced cell-extra cellular matrix adhesions and deficient cell-cell junctions, whereas long-t erm treatment with EGF induced a decrease of focal contact number and estab lishment of cell-cell junctions, resulting in downregulation of K14 and P-c adherin expression at the protein and mRNA levels. To determine whether cel l-extracellular matrix interactions mediated by integrins have a role in th e regulation of the expression of K14 and P-cadherin, the amounts of transc ripts for the two proteins were analysed in the basal cells, which were pla ted on the function-blocking antibodies against beta 1 and alpha 6 integrin chains, on fibronectin and on laminin 5, The amount of P-cadherin transcri pt was 2- to 4-fold higher in cells plated on the function-blocking anti-in tegrin antibodies and on the extracellular matrix proteins, as compared to cells plated on poly-l-lysine, whereas the K14 transcript levels were not s ignificantly modified in response to adhesion. The data demonstrate that in tegrin-mediated cell interaction with extracellular matrix is directly impl icated in the control of P-cadherin expression, and that EGF and cell-extra cellular matrix adhesion events are important regulators of the basal mamma ry epithelial cell phenotype.