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

Gustavo Baldassarre, Monica Fedele, Sabrina Battista, Andrea Vecchione, Andres J P Klein-Szanto, Massimo Santoro, Thomas A. Waldmann, Nazli Azimi, Carlo M. Croce, Alfredo Fusco

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)7970-7975
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number14
DOIs
Publication statusPublished - 2001

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ASJC Scopus subject areas

  • Genetics
  • General

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