Regulation of membrane-type 1 matrix metalloproteinase activity by vacuolar H+-ATPasesMaquoi, Erik ; ; Noël, Agnès et alin Biochemical Journal (2003), 373(Pt 1), 19-24 Membrane-type I matrix metalloprotemase (MT1-MMP) is a key enzyme in normal development and malignant processes. The regulation of MT1-MMP activity on the cell surface is a complex process involving ... [more ▼] Membrane-type I matrix metalloprotemase (MT1-MMP) is a key enzyme in normal development and malignant processes. The regulation of MT1-MMP activity on the cell surface is a complex process involving autocatalytic processing, tissue inhibitor of MMPs (TIMP) binding and constitutive internalization. However, the fate of internalized MT1-MMP is not known. Acidification of intracellular vacuolar compartments is essential for membrane trafficking, protein sorting and degradation. This acidification is controlled by vacuolar H+-ATPases, which can be selectively inhibited by bafilomycin-A(1). Here, we treated human tumour cell lines expressing MT1-MMP with bafilomycin-A(1), and analysed its effects on MT1-MMP activity, internalization and processing. We show that the activity of MT1-MMP on the cell surface is constitutively down-regulated through a vacuolar HI-ATPase-dependent degradation process. Blockade of this degradation caused the accumulation of TIMP-free active MT1-MMP molecules on the cell surface, although internalization was not affected. As a consequence of this impaired degradation, pro-MMP-2 activation was strongly enhanced. This study demonstrates that the catalytic activity of MT1-MMP on the cell surface is regulated through a vacuolar H+-ATPase-dependent degradation process. [less ▲] Detailed reference viewed: 8 (0 ULg) Effects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivoDesreux, Joëlle ; ; Noël, Agnès et alin Breast (Edinburgh, Scotland ) (2003), 12(2), 142-149 Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis ... [more ▼] Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer. (C) 2003 Elsevier Science Ltd. All rights reserved. [less ▲] Detailed reference viewed: 28 (2 ULg) |
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