NF-κB localization in multiple myeloma plasma cells and mesenchymal cells.
Several reports demonstrated that the activation of Nuclear Factor-kappa B NF-κB is essential for the pathogenesis of multiple myeloma (MM). We analyzed the nuclear localization of NF-κB in MM-cells derived from 60 different patients with MM at presentation and in relapse, as well as in three myeloma cell lines. Nuclear localization (the active form) of NF-κB was detected in only one MM-sample from a refractory patient and in two samples from relapsed patients, while all the other samples, including the MM-cell lines, almost exclusively express the cytoplasmic (inactive) form of NF-κB. In mesenchymal cells from MM-patients NF-κB was clearly present in the nucleus. In addition, the proteasome inhibitor Bortezomib, which is described to antagonize NF-κB activity, had a consistent antitumor activity against both chemoresistant and chemosensitive MM-cells, regardless the NF-κB localization, thus suggesting the existence of other molecular targets of proteasome inhibitors in MM.
Conticello
Concetta
C
Department of Experimental Oncology, Mediterranean Institute of Oncology (IOM), Viagrande, Catania, Italy.
Giuffrida
Raffaella
R
Adamo
Luana
L
Anastasi
Gabriele
G
Martinetti
Daniela
D
Salomone
Edvige
E
Colarossi
Cristina
C
Amato
Gabriella
G
Gorgone
Ausilia
A
Romano
Alessandra
A
Iannolo
Gioacchin
G
De Maria
Ruggero
R
Giustolisi
Rosario
R
Gulisano
Massimo
M
Di Raimondo
Francesco
F
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology
D000970:Antineoplastic Agents; D001897:Boronic Acids; D016328:NF-kappa B; D011719:Pyrazines; D000069286:Bortezomib