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Laminin and estradiol regulation of the plasminogen-activator system in MCF-7 breast-carcinoma cells

✍ Scribed by Shigueko Sonohara; Rafael Mira-Y-Lopez; M. Mitzi Brentani

Publisher: John Wiley and Sons
Year: 1998
Tongue: French
Weight: 421 KB
Volume: 76
Category: Article
ISSN: 0020-7136
DOI: 10.1002/(sici)1097-0215(19980330)76:1<77::aid-ijc13>3.0.co;2-d

No coin nor oath required. For personal study only.

✦ Synopsis

We have investigated the effects of laminin, on the plasminogen-activator system of MCF-7 breast-carcinoma cells. MCF-7 cells were incubated on plastic or laminin-coated wells, and medium and cell lysate aliquots were assayed for tissue-type (tPA) and urokinase-type plasminogen activator (uPA) by a chromogenic assay in combination with anti-uPA antibodies. Cells cultured on laminin displayed a 5-fold increase in tPA activity and a 2-fold decrease in uPA activity relative to cells on plastic. These effects could be mimicked by laminin fragment P1 but not by collagen I or fibronectin. tPA activity of cells treated with estradiol (10 nM) was 3-fold higher, that of cells on laminin treated with estradiol was 15-fold higher, than that of control. Northern-blot analysis showed that tPA mRNA levels were up-regulated by estradiol and laminin, whereas PAI-1 mRNA levels were down-regulated by laminin and not affected by E2. Concomitant treatment with laminin and estradiol, decreased PAI-1 mRNA and increased tPA mRNA levels, accounting for the synergistic increase in tPA activity. Laminin exerted only a modest (approx. 2-fold) inhibitory effect on uPA mRNA levels. In the breastcarcinoma cell line MDA-MB-231, down-regulation of PAI-1 and uPA mRNA by laminin was not observed. Adhesion assays indicated that ␣2␤1 is the predominant receptor for laminin in MCF-7 cells. MDA-MB-231 cells expressed ␣2 (54%) but this integrin is not used as a laminin receptor. These results support a role for ␣2␤1 in mediating interactions of MCF-7 with LN.

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