title: Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts.
abstract: When treated with the synthetic glucocorticoid dexamethasone, HT1080 human fibrosarcoma cells show changes in morphology, adhesion, and the extracellular matrix. Dexamethasone treatment results in a tenfold increase in the rate of fibronectin biosynthesis in HT1080 cells and a twofold increase in untransformed, normal human fibroblasts. Maximal induction levels are attained within one cell generation, while decay of the response requires several cell cycles. Pulse-chase studies showed that most of the newly synthesized fibronectin is secreted into the medium. The glucocorticoid antagonist, RU-486, blocks the dexamethasone-induced changes but does not alter the basal rate of fibronectin production. Therefore, fibronectin biosynthesis appears to be controlled by two distinct mechanisms--one, regulating basal rates of fibronectin production, which is transformation-sensitive and glucocorticoid-independent; and another, which is mediated by the glucocorticoid receptor, resulting in elevated rates of fibronectin biosynthesis upon dexamethasone treatment both in normal fibroblasts and in HT1080 cells.
mesh_terms: D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis*; D005354:Fibrosarcoma / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D005353:Fibronectins; D005938:Glucocorticoids; D007797:Laminin; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone