Oncogenic and anti-apoptotic activity of NF-κB in human thyroid carcinomas

Francesco Pacifico, Claudio Mauro, Ciro Barone, Elvira Crescenzi, Stefano Mellone, Mario Monaco, Gennaro Chiappetta, Giuseppe Terrazzano, Domenico Liguoro, Pasquale Vito, Eduardo Consiglio, Silvestro Formisano, Antonio Leonardi

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Thyroid cancer includes three types of carcinomas classified as differentiated thyroid carcinomas (DTC), medullary thyroid carcinomas, and undifferentiated carcinomas (UTC). DTC and medullary thyroid carcinomas generally have a good prognosis, but UTC are usually fatal. Consequently, there is a need for new effective therapeutic modalities to improve the survival of UTC patients. Here we show that NF-κB is activated in human thyroid neoplasms, particularly in undifferentiated carcinomas. Thyroid cell lines, reproducing in vitro the different thyroid neoplasias, also show basal NF-κB activity and resistance to drug-induced apoptosis, which correlates with the level of NF-κB activation. Activation of NF-κB in the DTC cell line NPA renders these cells resistant to drug-induced apoptosis. Stable expression of a super-repressor form of IκBα (IκBαM) in the UTC cell line FRO results in enhanced sensitivity to drug-induced apoptosis, to the loss of the ability of these cells to form colonies in soft agar, and to induce tumor growth in nude mice. In addition, we show that FRO cells display a very low JNK activity that is restored in FRO-IκBαM clones. Moreover, inhibition of JNK activity renders FRO-IκBαM clones resistant to apoptosis induced by chemotherapeutic agents. Our results indicate that NF-κB plays a pivotal role in thyroid carcinogenesis, being required for tumor growth and for resistance to drug-induced apoptosis, the latter function very likely through the inhibition of JNK activity. Furthermore, the strong constitutive NF-κB activity in human anaplastic thyroid carcinomas, besides representing a novel diagnostic tool, makes NF-κB a target for the development of novel therapeutic strategies.

Original languageEnglish
Pages (from-to)54610-54619
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
Publication statusPublished - Dec 24 2004

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Thyroid Neoplasms
Apoptosis
Carcinoma
Cells
Thyroid Gland
Pharmaceutical Preparations
Tumors
Drug Resistance
Cell Line
Chemical activation
Clone Cells
Neoplasms
Agar
Growth
Nude Mice
Human Activities
Carcinogenesis
Survival
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pacifico, F., Mauro, C., Barone, C., Crescenzi, E., Mellone, S., Monaco, M., ... Leonardi, A. (2004). Oncogenic and anti-apoptotic activity of NF-κB in human thyroid carcinomas. Journal of Biological Chemistry, 279(52), 54610-54619. https://doi.org/10.1074/jbc.M403492200

Oncogenic and anti-apoptotic activity of NF-κB in human thyroid carcinomas. / Pacifico, Francesco; Mauro, Claudio; Barone, Ciro; Crescenzi, Elvira; Mellone, Stefano; Monaco, Mario; Chiappetta, Gennaro; Terrazzano, Giuseppe; Liguoro, Domenico; Vito, Pasquale; Consiglio, Eduardo; Formisano, Silvestro; Leonardi, Antonio.

In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54610-54619.

Research output: Contribution to journalArticle

Pacifico, F, Mauro, C, Barone, C, Crescenzi, E, Mellone, S, Monaco, M, Chiappetta, G, Terrazzano, G, Liguoro, D, Vito, P, Consiglio, E, Formisano, S & Leonardi, A 2004, 'Oncogenic and anti-apoptotic activity of NF-κB in human thyroid carcinomas', Journal of Biological Chemistry, vol. 279, no. 52, pp. 54610-54619. https://doi.org/10.1074/jbc.M403492200
Pacifico, Francesco ; Mauro, Claudio ; Barone, Ciro ; Crescenzi, Elvira ; Mellone, Stefano ; Monaco, Mario ; Chiappetta, Gennaro ; Terrazzano, Giuseppe ; Liguoro, Domenico ; Vito, Pasquale ; Consiglio, Eduardo ; Formisano, Silvestro ; Leonardi, Antonio. / Oncogenic and anti-apoptotic activity of NF-κB in human thyroid carcinomas. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 52. pp. 54610-54619.
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AU - Mauro, Claudio

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AU - Mellone, Stefano

AU - Monaco, Mario

AU - Chiappetta, Gennaro

AU - Terrazzano, Giuseppe

AU - Liguoro, Domenico

AU - Vito, Pasquale

AU - Consiglio, Eduardo

AU - Formisano, Silvestro

AU - Leonardi, Antonio

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