Context: We have recently shown that NF-B activity is constitutively elevated in anaplastic human thyroid carcinomas. The inhibition of NF-B in the anaplastic thyroid carcinoma cell line FRO leads to increased susceptibility to apoptosis induced by chemotherapeutic drugs and to the block of oncogenic activity.

Objectives: To better understand the molecular mechanisms played by NF-B in thyroid oncogenesis, we performed a differential proteomic analysis between FRO IBM clones, in which NF-B activity is blocked, and the parental counterpart (FRO Neo cells).

Results: Differential proteomic analysis revealed that the Retinoblastoma associated protein 48 (RbAp48) is down-regulated in the absence of functional NF-B. Immunohistochemical analysis of normal and pathological human thyroid specimens confirmed that RbAp48 is strongly over-expressed in primary human carcinomas. Reduction of RbAp48 expression by using siRNA determined the suppression of tumorigenicity, very likely due to the decrease of their growth rate rather than to an increased susceptibility to apoptosis. In addition, we showed that RbAp 48 is, at least in part, transcriptionally controlled by NF-B. A functional NF-B consensus sequence was located within the promoter region of RbAp48 human gene, and embryonic fibroblasts isolated from the p65 knock out mouse (MEFs p65^-/-) showed decreased expression of RbAp48.

Conclusion: Our results demonstrate that RbAp48 is a NF-B-regulated gene playing an important role in thyroid cancer cell autonomous proliferation.