REGULATION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR PRODUCTION BY RAT MAMMARY MYOEPITHELIAL CELLS

Addition of basic fibroblast growth factor (bFGF) to a rat mammary gla nd myoepithelial cell line (25.5-G4.2.3) resulted in a six- to eightfo ld increase in cellular and secreted urokinase-type plasminogen activa tor (uPA) activity after a lap phase of 5-8 h. bFGF had no effect on t he uPA activity of mammary epithelial cells. bFGF was active on myoepi thelial cells over a narrow concentration range (0.5-2 ng/ml). The bFG F-induced increase in uPA activity was inhibited in a dose-dependent m anner by hydrocortisone and transforming growth factor-beta 1 (TGF-bet a 1). Hydrocortisone also inhibited the basal secretion of uPA, as did interleukin-1 beta and phorbol myristate acetate, both of which incre ase uPA levels in other cell systems, The effects of bFGF could also b e inhibited by factors which bind bFGF, e.g., heparin and methylamine a(2)-macroglobulin. TGF-beta 1, but not bFGF, induced the synthesis of plasminogen activator inhibitor-1 in the myoepithelial cell line. Mam mary gland myoepithelial cells contribute to the synthesis of and are located next to the basement membrane. Myoepithelial-derived uPA is pr obably associated with basement membrane turnover. The mammary gland b asement membrane undergoes many cycles of remodeling and multiple mech anisms may be required to regulate uPA activity. (C) 1996 Academic Pre ss, Inc.