INCREASE IN AP-1 ACTIVITY IS A GENERAL EVENT IN THYROID-CELL TRANSFORMATION IN-VITRO AND IN-VIVO

We have recently reported that neoplastic transformation of two rat th yroid epithelial cell lines by retroviruses carrying the v-mos and v-r as Ki oncogenes is associated with a drastic increase of AP-1 activity . The most important effects were represented by the dramatic junB and fra-1 gene induction, which was abolished by the block of the transfo rmation-induced HMGI-C protein synthesis. Here, we have further charac terized the transformation-dependent AP-1 activity, by analysing the e xpression of different jun- and fos-related components, in rat thyroid cell lines transformed by several oncogenes, in human thyroid carcino ma cell lines, and in naturally occurring human thyroid rumours. A sig nificant increase of Fra-1 and JunB protein levels was detected in all oncogene transformed rat thyroid cell lines, Fra-1 gene induction was demonstrated to occur also in human thyroid carcinoma cell lines and tissues, Conversely, c-Jun and JunD proteins, rather than JunB, accumu lated in human thyroid carcinoma cell lines. An induction of AP-1 targ et genes was also detected both in rat and human thyroid transformed c ell lines. Therefore, in vivo and in vitro thyroid cell transformation is associated with important compositional changes in the AP-1 comple x and an increased transcriptional activity.