Iannetti, Alessio (2008) The Neutrophil Gelatinase-associated lipocalin (NGAL), a NF-kB regulated gene, is a survival factor for thyroid neoplastic cells. [Tesi di dottorato] (Inedito)

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: The Neutrophil Gelatinase-associated lipocalin (NGAL), a NF-kB regulated gene, is a survival factor for thyroid neoplastic cells
Autori:
AutoreEmail
Iannetti, AlessioJollyblue81@hotmail.com
Data: 1 Dicembre 2008
Numero di pagine: 64
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Biologia e patologia cellullare e molecolare "L. Califano"
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 21
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricoavvedim@unina.it
Tutor:
nomeemail
Formisano, Silvestrosilvestr@unina.it
Leonardi, Antonioantonio.leonardi@unina.it
Data: 1 Dicembre 2008
Numero di pagine: 64
Parole chiave: NGAL, NF-kB, Cancer
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Depositato il: 12 Nov 2009 14:23
Ultima modifica: 30 Apr 2014 19:36
URI: http://www.fedoa.unina.it/id/eprint/3277
DOI: 10.6092/UNINA/FEDOA/3277

Abstract

ABSTRACT NF-κB is constitutively activated in primary human thyroid tumors, particularly in those of anaplastic type. The inhibition of NF-κB activity in the human anaplastic thyroid carcinoma cell line, FRO, leads to an increased susceptibility to chemotherapeutic drug-induced apoptosis and to the blockage of their ability to form tumors in nude mice. To identify NF-κB target genes involved in thyroid cancer, we analyzed the secretome of conditioned media from parental and NF-κB-null FRO cells. Proteomic analysis revealed that the neutrophil gelatinase-associated lipocalin (NGAL), a protein involved in inflammatory and immune responses, is secreted by FRO cells whereas its expression is strongly reduced in the NF-κB-null FRO cells. NGAL is highly expressed in human thyroid carcinomas, and knocking down its expression blocks the ability of FRO cells to grow in soft agar and form tumors in nude mice. These effects are reverted by the addition of! either recombinant NGAL or FRO conditioned medium. In addition, we show that the prosurvival activity of NGAL is mediated by its ability to bind and transport iron inside the cells. Our data suggest that NF-κB contributes to thyroid tumor cell survival by controlling iron uptake via NGAL.

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