LAMININ AND TENASCIN ASSEMBLY AND EXPRESSION REGULATE HC11 MOUSE MAMMARY CELL-DIFFERENTIATION

HC11 is a normal mouse mammary epithelial cell line that requires cert ain growth factors, such as EGF or bFGF, to respond optimally to lacto genic hormones and produce the differentiation marker beta-casein. Gro wth in insulin (Ins) or PDGF does not produce cells competent to respo nd to lactogenic hormones. Here we show that competency for differenti ation is due at least in part to the modulation of extracellular matri x components. In particular we have studied laminin and tenascin. EGF alters endogenous laminin assembly. In addition, promotion of competen cy can be partially mimicked by plating HC11 cells on the E8 laminin f ragment, which is able to induce lactogenic responsiveness in cells gr own in the absence of EGF or bFGF. The production and assembly of tena scin is also dependent upon the growth conditions of the HC11 cells. E GF- or bFGF-grown competent cells produce tenascin but do not assemble it at the extracellular matrix as efficiently as Ins- or PDGF-grown, non-competent cells. This alteration apparently leads to a change in t he cellular microenvironment that supports beta-casein production. In addition, when competent cells are plated on dishes coated with tenasc in, lactogenic hormone induction of beta-casein is inhibited. The data suggest that tenascin assembly and beta-casein production are opposin g features of a coordinated differentiation program of HC11 cells.