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[Cancer Research 59, 4793-4797, October 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 4793-4797, October 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

The Expression of a Truncated HMGI-C Gene Induces Gigantism Associated with Lipomatosis

Sabrina Battista, Vincenzo Fidanza, Monica Fedele, Andres J. P. Klein-Szanto, Eric Outwater, Han Brunner, Massimo Santoro, Carlo M. Croce and Alfredo Fusco1

Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [S. B., V. F., M. F., C. M. C.]; Dipartimento di Biologia e Patologia Cellulare e Molecolare, c/o Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy [S. B., M. F., M S.]; Experimental Histopathology, Fox-Chase Cancer Center, Philadelphia, Pennsylvania 19111 [A. J. P. K-S.]; Image Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107 [E. O.]; Department of Clinical Genetics, University Hospital Nijmegen, 417 Nijmegen, the Netherlands [H. B.]; and Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università di Catanzaro, 88100 Catanzaro, Italy [A. F.]

Rearrangements of the HMGI-C gene have frequently been detected in human benign tumors of mesenchymal origin, including lipomas. The HMGI-C protein has three AT-hook domains and an acidic COOH-terminal tail. The HMGI-C modifications consist in the loss of the C-tail and the fusion with ectopic sequences. Recent results show that the loss of the COOH-terminal region, rather than the acquisition of new sequences, is sufficient to confer to HMGI-C the ability to transform NIH3T3 cells. Therefore, transgenic mice carrying a HMGI-C construct (HMGI-C/T), containing only the three AT-hook domains, were generated. The HMGI-C/T mice showed a giant phenotype, together with a predominantly abdominal/pelvic lipomatosis, suggesting a pivotal role of the HMGI-C truncation in the generation of human lipomas.




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