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.
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.
Baldassarre
G
G
Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19107, USA.
Fedele
M
M
Battista
S
S
Vecchione
A
A
Klein-Szanto
A J
AJ
Santoro
M
M
Waldmann
T A
TA
Azimi
N
N
Croce
C M
CM
Fusco
A
A
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
D006609:High Mobility Group Proteins; D019409:Interleukin-15; D007376:Interleukin-2