Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product

Publisher Website
Google Scholar
Abstract
The expression of the high mobility group I (HMGI)‐C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI‐C gene product, we have analyzed the AP‐1 complex in normal, fully transformed and antisense HMGI‐C‐expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP‐1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra‐1 gene induction, which is prevented in cell lines expressing the antisense HMGI‐C. These results indicate that the HMGI‐C gene product is essential for the junB and fra‐1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra‐1 protein synthesis by stable transfection with a fra‐1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra‐1 gene product in the process of cellular transformation.