Regulation of urokinase-type plasminogen activator production by rat mammary myoepithelial cells.
Addition of basic fibroblast growth factor (bFGF) to a rat mammary gland myoepithelial cell line (25.5-G4.2.3) resulted in a six- to eightfold increase in cellular and secreted urokinase-type plasminogen activator (uPA) activity after a lag phase of 5-8 h. bFGF had no effect on the uPA activity of mammary epithelial cells. bFGF was active on myoepithelial cells over a narrow concentration range (0.5-2 ng/ml). The bFGF-induced increase in uPA activity was inhibited in a dose-dependent manner by hydrocortisone and transforming growth factor-beta1 (TGF-beta1). Hydrocortisone also inhibited the basal secretion of uPA, as did interleukin-1beta and phorbol myristate acetate, both of which increase uPA levels in other cell systems. The effects of bFGF could also be inhibited by factors which bind bFGF, e.g., heparin and methylamine a2-macroglobulin. TGF-beta1, but not bFGF, induced the synthesis of plasminogen activator inhibitor-1 in the myoepithelial cell line. Mammary gland myoepithelial cells contribute to the synthesis of and are located next to the basement membrane. Myoepithelial-derived uPA is probably associated with basement membrane turnover. The mammary gland basement membrane undergoes many cycles of remodeling and multiple mechanisms may be required to regulate uPA activity.
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
M J
MJ
Warburton
S R
SR
Dundas
B A
BA
Gusterson
M J
MJ
O'Hare
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010960:Plasminogen Activators / Q000096:biosynthesis*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D016207:Cytokines; D006133:Growth Substances; D006728:Hormones; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone