title: The neutrophil gelatinase-associated lipocalin (NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells.
abstract: NF-kappaB is constitutively activated in primary human thyroid tumors, particularly in those of anaplastic type. The inhibition of NF-kappaB 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-kappaB target genes involved in thyroid cancer, we analyzed the secretome of conditioned media from parental and NF-kappaB-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-kappaB-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-kappaB contributes to thyroid tumor cell survival by controlling iron uptake via NGAL.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II University of Naples, via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Iannetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Pacifico
authors.forename: Renato
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lavorgna
authors.forename: Elvira
authors.initials: E
authors.lastname: Crescenzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Vascotto
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Salzano
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Emilia
authors.initials: E
authors.lastname: Vuttariello
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Silvestro
authors.initials: S
authors.lastname: Formisano
authors.forename: Antonio
authors.initials: A
authors.lastname: Leonardi