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Glucocorticoid modulation of plasminogen activators and of one of their inhibitors in the human mammary carcinoma cell line MDA-MB-231

Busso, N.
Failly-Crepin, C.
Published in Cancer Research. 1987, vol. 47, no. 2, p. 364-370
Abstract In cultures of the human mammary carcinoma-derived cell line MDA-MB-231, plasminogen activator (PA) activity was reduced substantially following treatment with the glucocorticoid dexamethasone. These cells produced urokinase-type PA (u-PA) and tissue-type PA (t-PA), and both enzymes were decreased in dexamethasone-treated cultures. The drop in u-PA activity was associated with a decrease in the synthesis of single-chain pro-u-PA and in the concentration of u-PA messenger RNA; however, the decrease in u-PA activity was more extensive than could be accounted for by inhibition of enzyme synthesis only, suggesting that postsynthetic events were also involved. The comparatively small dexamethasone-induced decrease in t-PA activity was not associated with a change in the concentration of t-PA messenger RNA. Hence, the two PA genes are differentially regulated by the same hormone. MDA-MB-231 cells also produced a PA-specific inhibitor related to that produced by bovine aortic endothelial cells (PAI-1). This inhibitor was present in two forms: one functionally active, and the other which required activation by sodium dodecyl sulfate; both forms were increased in cultures exposed to dexamethasone. Thus, glucocorticoid-induced inhibition of PA activity in these cells results from a decrease in u-PA synthesis and a concomitant increase in the production of a PA inhibitor.
Keywords Breast Neoplasms/ enzymologyCell LineDexamethasone/ pharmacologyGene Expression Regulation/drug effectsHumansPlasminogen Activators/antagonists & inhibitors/genetics/ metabolismPlasminogen InactivatorsProtease Inhibitors/geneticsRNA, Messenger/geneticsTissue Plasminogen Activator/genetics/metabolismUrokinase-Type Plasminogen Activator/genetics/metabolism
PMID: 3098408
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BUSSO, N. et al. Glucocorticoid modulation of plasminogen activators and of one of their inhibitors in the human mammary carcinoma cell line MDA-MB-231. In: Cancer Research, 1987, vol. 47, n° 2, p. 364-370. https://archive-ouverte.unige.ch/unige:8660

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Deposited on : 2010-07-12

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