Abstract
Overexpression of HMGA1 proteins is a constant feature of human carcinomas. Moreover, rearrangements of this gene have been detected in several human benign tumors of mesenchymal origin. To define the role of these proteins in cell transformation in vivo, we have generated transgenic mice overexpressing ubiquitously the HMGA1 gene. These mice developed mixed growth hormone/prolactin cell pituitary adenomas and natural killer (NK)-T/NK cell lymphomas. The HMGA1-induced expression of IL-2 and IL-15 proteins and their receptors may account for the onset of these lymphomas. At odds with mice overexpressing a wild-type or a truncated HMGA2 protein, adrenal medullar hyperplasia and pancreatic islet cell hyperplasia frequently occurred and no increase in body size and weight was observed in HMGA1 mice. Taken together, these data indicate an oncogenic role of the HMGA1 gene also in vivo.
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References
Abe N, Watanabe T, Masaki T, Mori T, Sugiyama M, Uchimura H, Fujioka Y, Chiappetta G, Fusco A and Atomi Y . (2000). Cancer Res., 60, 3117–3122.
Abe N, Watanabe T, Sugiyama M, Uchimura H, Chiappetta G, Fusco A and Atomi Y . (1999). Cancer Res., 59, 1169–1174.
Anand A and Chada K . (2000). Nat. Genet., 24, 377–380.
Arlotta P, Tai AK, Manfioletti G, Clifford C, Jay G and Ono SJ . (2000). J. Biol. Chem., 275, 14394–14400.
Ashar HR, Fejzo MS, Tkachenko A, Zhou X, Fletcher JA, Weremowicz S, Morton CC and Chada K . (1995). Cell, 82, 57–65.
Azimi N, Shiramizu KM, Tagaya Y, Mariner J and Waldmann TA . (2000). J. Virol., 74, 7338–7348.
Baldassarre G, Battista S, Belletti B, Thakur S, Pentimalli F, Trapasso F, Fedele M, Pierantoni GM, Croce CM and Fusco A . (2003). Mol. Cell. Biol., 23, 2225–2238.
Baldassarre G, Fedele M, Battista S, Vecchione A, Klein-Szanto AJ, Santoro M, Waldmann TA, Azimi N, Croce CM and Fusco A . (2001). Proc. Natl. Acad. Sci. USA, 98, 7970–7975.
Bandiera A, Bonifacio D, Manfioletti G, Mantovani F, Rustighi A, Zanconati F, Fusco A, Di Bonito L and Giancotti V . (1998). Cancer Res., 58, 426–431.
Battista S, Fidanza V, Fedele M, Klein-Szanto JP, Outwater E, Brunner H, Santoro M, Croce CM and Fusco A . (1999). Cancer Res., 59, 4793–4797.
Berlingieri MT, Manfioletti G, Santoro M, Bandiera A, Visconti R, Giancotti V and Fusco A . (1995). Mol. Cell. Biol., 15, 1545–1553.
Berlingieri MT, Pierantoni GM, Giancotti V, Santoro M and Fusco A . (2002). Oncogene, 21, 2971–2980.
Brunetti A, Manfioletti G, Chiefari E, Goldfine ID and Foti D . (2001). FASEB J., 15, 492–500.
Bustin M and Reeves R . (1996). Prog. Nucleic Acid Res. Mol. Biol., 54, 35–100.
Chiappetta G, Avvantaggiato V, Visconti R, Fedele M, Battista S, Trapasso F, Merciai BM, Fidanza V, Giancotti V, Santoro M, Simeone A and Fusco A . (1996). Oncogene, 13, 2439–2446.
Chiappetta G, Bandiera A, Berlingieri MT, Visconti R, Manfioletti G, Battista S, Martinez-Tello FJ, Santoro M, Giancotti V and Fusco A . (1995). Oncogene, 10, 1307–1314.
Chiappetta G, Manfioletti G, Pentimalli F, Abe N, Di Bonito M, Vento MT, Giuliano A, Fedele M, Viglietto G, Santoro M, Watanabe T, Giancotti V and Fusco A . (2001). Int. J. Cancer, 91, 147–151.
Chiappetta G, Tallini G, De Biasio MC, Manfioletti G, Martinez-Tello FJ, Pentimalli F, de Nigris F, Mastro A, Botti G, Fedele M, Berger N, Santoro M, Giancotti V and Fusco A . (1998). Cancer Res., 58, 4193–4198.
Di Noto R, Pane F, Camera A, Luciano L, Barone M, Lo Pardo C, Boccuni P, Intrieri M, Izzo B, Villa MR, Macri M, Rotoli B, Sacchetti L, Salvatore F and Del Vecchio L . (2001). Leukemia, 15, 1641–1649.
Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, Casamassimi A, Santoro M, Giancotti V and Fusco A . (1996). Cancer Res., 56, 1896–1901.
Fedele M, Battista S, Kenyon L, Baldassarre G, Fidanza V, Klein-Szanto AJ, Parlow AF, Visone R, Pierantoni GM, Outwater E, Santoro M, Croce CM and Fusco A . (2002). Oncogene, 21, 3190–3198.
Fedele M, Berlingieri MT, Scala S, Chiariotti L, Viglietto G, Rippel V, Bullerdiek J, Santoro M and Fusco A . (1998). Oncogene, 17, 413–418.
Fehniger TA, Suzuki K, Ponnappan A, VanDeusen JB, Cooper MA, Florea SM, Freud AG, Robinson ML, Durbin J and Caligiuri MA . (2001). J. Exp. Med., 193, 219–231.
Finelli P, Pierantoni GM, Giardino D, Losa M, Rodeschini O, Fedele M, Valtorta E, Mortini P, Croce CM, Larizza L and Fusco A . (2002). Cancer Res., 62, 2398–2405.
Himes SR, Coles LS, Reeves R and Shannon MF . (1996). Immunity, 5, 479–489.
Hogan B . (1983). Nature, 306, 313–314.
Johnson KR, Lehn DA and Reeves R . (1989). Mol. Cell. Biol., 9, 2114–2123.
Melillo RM, Pierantoni GM, Scala S, Stella A, Battista S, De Biasio MC, Fedele M, Chiappetta G, Fidanza V, Condorelli G, Santoro M, Croce CM, Viglietto G and Fusco A . (2001). Mol. Cell. Biol., 21, 2485–2495.
Reeves R, Edberg DD and Li Y . (2001). Mol. Cell. Biol., 21, 575–594.
Scala S, Portella G, Fedele M, Chiappetta G and Fusco A . (2000). Proc. Natl. Acad. Sci. USA, 97, 4256–4261.
Schoenmakers EFPM, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H and Van de Ven WJM . (1995). Nat. Genet., 10, 436–443.
Tamimi Y, van der Poel HG, Denyn MM, Umbas R, Karthaus HF, Debruyne FM and Schalken JA . (1993). Cancer Res., 53, 5512–5516.
Thanos D and Maniatis T . (1992). Cell, 71, 777–789.
Tkachenko A, Ashar HR, Meloni AM, Sandberg AA and Chada KK . (1997). Cancer Res., 57, 2276–2280.
Wood LJ, Maher JF, Bunton TE and Resar LM . (2000). Cancer Res., 60, 4256–4261.
Xiao S, Lux ML, Reeves R, Hudson TJ and Fletcher JA . (1997). Am. J. Pathol., 150, 901–910.
Zhou X, Benson KF, Ashar HR and Chada K . (1995). Nature (London), 376, 771–774.
Acknowledgements
We are grateful to Andrea Affuso for his helpful advices about mice management, Antonio Luciano for the animal care and Dario Palmieri for the technical assistance. We thank Fabrizio Pane for the DERL-7 cell line and the Associazione Partenopea per le Ricerche Oncologiche (APRO) for its support. This work was also supported by grants from AIRC and MURST, projects ‘Terapie antineoplastiche innovative’ and ‘Piani di Potenziamento della Rete Scientifica e Tecnologica’. We are grateful to Jean Ann Gilder for editing the text.
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Fedele, M., Pentimalli, F., Baldassarre, G. et al. Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas. Oncogene 24, 3427–3435 (2005). https://doi.org/10.1038/sj.onc.1208501
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DOI: https://doi.org/10.1038/sj.onc.1208501
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