Posttranscriptional down-regulation of fibronectin in N-ras-transformed cells.

The basal level of fibronectin (FN) biosynthesis is greatly reduced in N-ras-transformed human fibrosarcoma HT1080 cells when compared with normal fibroblasts. The rate of FN biosynthesis can be significantly increased in HT1080 cells by the synthetic glucocorticoid dexamethasone, which has been shown to act by selectively stabilizing the FN message (D.C. Dean, R.F. Newby, and S. Bourgeois, J. Cell Biol., 106: 2159-2170, 1988). The present study demonstrates that the basal levels of FN biosynthesis and accumulated FN mRNA are also reduced in HT1080 cells when compared with nontumorigenic revertants of HT1080 cells in which the mutated N-ras allele is underrepresented. In contrast, the FN promoter is more active in HT1080 cells than in the revertant cells. These results indicate that the down-regulation of FN in HT1080 cells is linked to expression of the N-ras oncogene and that the effect is posttranscriptional. Therefore, the N-ras oncogene and glucocorticoids have opposite posttranscriptional effects on FN biosynthesis in HT1080 cells. However, this study demonstrates that the stimulatory effects of glucocorticoids are not mediated by a transcriptional repression of the N-ras gene.