EXPRESSION OF THE NEOPLASTIC PHENOTYPE BY HUMAN THYROID-CARCINOMA CELL-LINES REQUIRES NF-KAPPA-B P65 PROTEIN EXPRESSION

We have investigated the role of the NF kappa B complex in the process of thyroid carcinogenesis by analysing thyroid carcinoma cell lines, A significant increase in p65 NF kappa B mRNA and protein expression, compared to normal thyroid cultures or tissue, was found in all of the cancer cell lines, Conversely, only a modest increase in the p50 NF k appa B mRNA and protein was found in most, but not all carcinoma cell lines, The block of p65 protein synthesis with specific antisense olig onucleotides greatly reduced the ability of two undifferentiated carci noma cell lines to form colonies in agar and reduced their growth rate , On the other hand, no effect was observed in the same cell lines whe n treated with p50 specific antisense oligonucleotides. These inhibito ry effects seem to be mediated by the suppression of c-myc gene expres sion, since treatment with antisense oligonucleotides for p65 gene int erfered negatively with c-myc gene expression, Our results indicate th at activation of the NF kappa B complex by overexpression of p65 plays a critical role in the process of thyroid cell transformation.