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. 1988 Jun 1;106(6):2159–2170. doi: 10.1083/jcb.106.6.2159

Regulation of fibronectin biosynthesis by dexamethasone, transforming growth factor beta, and cAMP in human cell lines

PMCID: PMC2115148  PMID: 2454932

Abstract

The regulation of fibronectin (FN) biosynthesis by dexamethasone (a synthetic glucocorticoid), forskolin (an activator of adenylate cyclase), and transforming growth factor beta (TGF-beta) was examined in six human cell lines. Dexamethasone treatment produced the largest increase in FN biosynthesis in the fibrosarcoma cell line, HT-1080 (approximately 45-fold). This seems to result from a dexamethasone- mediated increase in FN mRNA stability which increases the message half- life from approximately 11 to 26 h. The relative instability of FN mRNA in the fibrosarcoma (t1/2 11 h) compared to normal fibroblasts (70 h) appears to result from the particular transformed phenotype of the HT- 1080 cells. Forskolin and TGF-beta increase the rate of FN gene transcription in most of the cell lines. These effects (four- to six- fold) occur rapidly and do not require protein synthesis in the responsive cell lines which include normal fibroblasts. However, in the fibrosarcoma (HT-1080), a surprisingly large induction (20-30-fold) is observed and this induction is different from that in the normal fibroblasts and the other cell lines in that both protein synthesis and a lag period are required. Synergism is seen with dexamethasone and either forskolin or TGF-beta in HT-1080 cells increasing the rate of FN biosynthesis approximately 200-fold to a level similar to normal fibroblasts. This seems to result from a combination of FN mRNA stabilization (dexamethasone) and increased transcription (forskolin and TGF-beta).

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Selected References

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