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Environmental influences on the activity of plasminogen activator inhibitor‐1
Author(s) -
Gibbons Jennifer A.,
Church Frank C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb64
Subject(s) - plasminogen activator , plasmin , adipokine , angiogenesis , cancer research , motility , metastasis , urokinase , plasminogen activator inhibitor 1 , endocrinology , chemistry , medicine , cancer , biology , microbiology and biotechnology , insulin , biochemistry , insulin resistance , enzyme
The typical Western diet is high in fat, and there is evidence of a higher incidence of breast cancer in U.S. women due to this diet. Adipocytokines regulate expression of many proteins that are expressed in both adipocytes and breast cancer cells, including plasminogen activator inhibitor‐1 (PAI‐1) and urokinase plasminogen activator (uPA). PAI‐1 inhibits uPA, which blocks plasmin generation and regulates fibrinolysis. In addition, PAI‐1 is involved in cell motility and angiogenesis. Due to these broad biological abilities PAI‐1 is involved both in carcinogenesis and in invasion‐metastasis, although the exact mechanisms are unclear. We have analyzed the effects of insulin, IGF‐1, TNFα, glucose, and IL‐6 in the breast cancer cell lines MDA‐MB‐231 and MCF10AT, using uPA activity assays to measure the balance of uPA and PAI‐1 and western blots. Adipocytokines do not alter cell viability at the concentrations being used. IGF‐1 and IL‐6 increase uPA activity in MDA‐MB‐231’s, while causing no change in MCF10AT’s. In addition, TNFα decreases uPA activity in the MDA‐MB‐231’s yet increases the same activity in MCF10ATs. These effects will be further studied using cell motility assays. We believe that a methodological study of these cell lines will help us understand the role of the plasminogen activator system in cancer. Supported by Susan G. Komen Breast Cancer Foundation BCTR45206 (FCC) and NIEHS 5‐T32ES07017‐33 (JAG).