1. Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NFkappaB p65 protein expression
- Author
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Francesco Curcio, Roberta Visconti, Kazuya Zeki, Francesco Trapasso, Filomena de Nigris, Sabrina Battista, Maria Pia Miano, Massimo Santoro, Janete Cerutti, Laura Casalino, Alfredo Fusco, Monica Fedele, R., Visconti, J., Cerutti, S., Battista, M., Fedele, F., Trapasso, K., Zeki, M. P., Miano, F. d., Nigri, L., Casalino, F., Curcio, Santoro, Massimo, Fusco, Alfredo, Visconti, R, Cerutti, J, Battista, S, Fedele, M, Trapasso, F, Zeki, K, Miano, Mp, de NIGRIS, Filomena, Casalino, L, Curcio, F, Santoro, M, and Fusco, A.
- Subjects
Cancer Research ,genetics/metabolism, Tumor Cell ,Genes, myc ,Down-Regulation ,Biology ,medicine.disease_cause ,drug effects, Gene Expression Regulation ,Thyroid carcinoma ,Gene expression ,Genetics ,medicine ,Protein biosynthesis ,Neoplastic, Gene ,Tumor Cells, Cultured ,Humans ,pharmacology, Phenotype, Protein Synthesis Inhibitor ,Thyroid Neoplasms ,Antisense ,Molecular Biology ,Gene ,Protein Synthesis Inhibitors ,Messenger RNA ,Cultured ,Thyroid ,NF-kappa B ,Oligonucleotides, Antisense ,myc, Humans, NF-kappa B ,pharmacology, Thyroid Neoplasm ,biosynthesis/genetics, Oligonucleotide ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Phenotype ,Cell culture ,Immunology ,Cancer research ,Carcinogenesis - Abstract
We have investigated the role of the NFkappaB complex in the process of thyroid carcinogenesis by analysing thyroid carcinoma cell lines. A significant increase in p65 NFkappaB 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 NFkappaB mRNA and protein was found in most, but not all carcinoma cell lines. The block of p65 protein synthesis with specific antisense oligonucleotides greatly reduced the ability of two undifferentiated carcinoma 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 when treated with p50 specific antisense oligonucleotides. These inhibitory effects seem to be mediated by the suppression of c-myc gene expression, since treatment with antisense oligonucleotides for p65 gene interfered negatively with c-myc gene expression. Our results indicate that activation of the NFkappaB complex by overexpression of p65 plays a critical role in the process of thyroid cell transformation.
- Published
- 1997