title: Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway.
abstract: Rearrangements of the high mobility group protein I-C (HMGI-C) gene, consisting in the loss of the carboxyl-terminal tail, have been frequently detected in benign human tumors of mesenchymal origin. We have previously demonstrated that transgenic (TG) mice carrying a truncated HMGI-C construct (HMGI-C/T) exhibit a giant phenotype together with a predominantly abdominal/pelvic lipomatosis. Here, we report that HMGI-C/T TG mice develop natural killer (NK)-T/NK cell lymphomas starting from 12 months of age. We found an increased expression of IL-2 and IL-15 proteins and their receptors in these lymphomas, and we demonstrate that HMGI-C/T protein positively regulates their expression in vitro. Therefore, the HMGI-C/T-mediated chronic stimulation of the IL-2/IL-15 pathway could be responsible for the onset of NK-T/NK cell lymphomas in HMGI-C/T TG mice.
authors: Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
authors: G
authors: G
authors: Baldassarre
authors: M
authors: M
authors: Fedele
authors: S
authors: S
authors: Battista
authors: A
authors: A
authors: Vecchione
authors: A J
authors: AJ
authors: Klein-Szanto
authors: M
authors: M
authors: Santoro
authors: T A
authors: TA
authors: Waldmann
authors: N
authors: N
authors: Azimi
authors: C M
authors: CM
authors: Croce
authors: A
authors: A
authors: Fusco
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D006609:High Mobility Group Proteins; D019409:Interleukin-15; D007376:Interleukin-2