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.
Bibliographical noteFunding Information:
Thus work was supported by grant 5-ROI-GM20868 from the National Institutes of General Medical Sciences and a grant from the Pardee Foundation to S. B., and grants CA 21463 and CA 29995 from the National Cancer Institute and the National Institutes of Health and by the Leukemia Task Force, University of Minnesota to L. T. F. N. 0. is the recipient of fellowship PF-2109 from the American Cancer Society, and L. T. F. is a recipient of the Stone Professorship in Pathology, University of Minnesota, and Research Career Development Award CA 00651 from the National Career Institute and the National Institutes of Health.