TY - JOUR
T1 - RbAp48 is a target of nuclear factor-κB activity in thyroid cancer
AU - Pacifico, Francesco
AU - Paolillo, Michele
AU - Chiappetta, Gennaro
AU - Crescenzi, Elvira
AU - Arena, Simona
AU - Scaloni, Andrea
AU - Monaco, Mario
AU - Vascotto, Carlo
AU - Tell, Gianluca
AU - Formisano, Silvestro
AU - Leonardi, Antonio
PY - 2007/4
Y1 - 2007/4
N2 - Context: We have recently shown that nuclear factor (NF)-κB activity is constitutively elevated in anaplastic human thyroid carcinomas. The inhibition of NF-κB 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 understand better the molecular mechanisms played by NF-κB in thyroid oncogenesis, we performed a differential proteomic analysis between FRO transfected with a superrepressor form of inhibitor of κBα (IκBαM) 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-κB. Immunohistochemical analysis of normal and pathological human thyroid specimens confirmed that RbAp48 is strongly overexpressed in primary human carcinomas. Reduction of RbAp48 expression using small interfering RNA 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 NF-κB, at least in part, transcriptionally controls RbAp 48. A functional NF-κB consensus sequence was located within the promoter region of RbAp48 human gene, and embryonic fibroblasts isolated from the p65 knockout mouse (murine embryonic fibroblasts p65-/-) showed decreased expression of RbAp48. Conclusion: Our results show that RbAp48 is a NF-κB-regulated gene playing an important role in thyroid cancer cell autonomous proliferation.
AB - Context: We have recently shown that nuclear factor (NF)-κB activity is constitutively elevated in anaplastic human thyroid carcinomas. The inhibition of NF-κB 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 understand better the molecular mechanisms played by NF-κB in thyroid oncogenesis, we performed a differential proteomic analysis between FRO transfected with a superrepressor form of inhibitor of κBα (IκBαM) 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-κB. Immunohistochemical analysis of normal and pathological human thyroid specimens confirmed that RbAp48 is strongly overexpressed in primary human carcinomas. Reduction of RbAp48 expression using small interfering RNA 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 NF-κB, at least in part, transcriptionally controls RbAp 48. A functional NF-κB consensus sequence was located within the promoter region of RbAp48 human gene, and embryonic fibroblasts isolated from the p65 knockout mouse (murine embryonic fibroblasts p65-/-) showed decreased expression of RbAp48. Conclusion: Our results show that RbAp48 is a NF-κB-regulated gene playing an important role in thyroid cancer cell autonomous proliferation.
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U2 - 10.1210/jc.2006-2199
DO - 10.1210/jc.2006-2199
M3 - Article
C2 - 17244783
AN - SCOPUS:34147132965
VL - 92
SP - 1458
EP - 1466
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -