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

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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

Fingerprint

High Mobility Group Proteins
Interleukin-15
Protein C
Natural Killer Cells
Transgenic Mice
Interleukin-2
Lymphoma
Genes
Natural Killer T-Cells
Tail
Proteins
Phenotype
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

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

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 14, 2001, p. 7970-7975.

Research output: Contribution to journalArticle

Baldassarre, Gustavo ; Fedele, Monica ; Battista, Sabrina ; Vecchione, Andrea ; Klein-Szanto, Andres J P ; Santoro, Massimo ; Waldmann, Thomas A. ; Azimi, Nazli ; Croce, Carlo M. ; Fusco, Alfredo. / 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. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 14. pp. 7970-7975.
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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.",
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AU - Baldassarre, Gustavo

AU - Fedele, Monica

AU - Battista, Sabrina

AU - Vecchione, Andrea

AU - Klein-Szanto, Andres J P

AU - Santoro, Massimo

AU - Waldmann, Thomas A.

AU - Azimi, Nazli

AU - Croce, Carlo M.

AU - Fusco, Alfredo

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