The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis.
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.
Battista
S
S
Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Fidanza
V
V
Fedele
M
M
Klein-Szanto
A J
AJ
Outwater
E
E
Brunner
H
H
Santoro
M
M
Croce
C M
CM
Fusco
A
A
D016475:3T3 Cells; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000473:pathology; D000818:Animals; D002678:Chimera; D015321:Gene Rearrangement; D005877:Gigantism / Q000235:genetics* / Q000473:pathology; D025743:HMGA2 Protein; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008068:Lipomatosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D013737:Testis / Q000033:anatomy & histology; D014162:Transfection; D001743:Urinary Bladder / Q000033:anatomy & histology
D025743:HMGA2 Protein; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins