Truncated and chimeric HMGI-C genes induce neoplastic transformation of NIH3T3 murine fibroblasts.
Overexpression of the high mobility group I (HMGI) proteins is often associated with the malignant phenotype. Moreover, many benign human tumors, mainly of mesenchymal origin, are characterized by rearrangements of the HMGI-C gene. In most cases, HMGI-C alterations involve breaks within the third intron of the gene resulting in aberrant transcripts carrying exons from 1-3, which encode the three DNA binding domains, fused to ectopic sequences. Here, we show that the expression of a truncated form of HMGI-C protein carrying only the three DNA-binding domains, or of a fusion protein carrying the three DNA-binding domains of HMGI-C and the LIM domains of the lipoma preferred partner gene (LPP) protein, causes malignant transformation of NIH3T3 cells. The unrearranged wild-type HMGI-C cDNA did not exert any transforming activity. These findings indicate that rearranged forms of HMGI-C play a role in cell transformation.
Istituto Nazionale dei Tumori di Napoli, Fondazione Senatore Pascale, Naples, Italy.
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M
Fedele
M T
MT
Berlingieri
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S
Scala
L
L
Chiariotti
G
G
Viglietto
V
V
Rippel
J
J
Bullerdiek
M
M
Santoro
A
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Fusco
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D006609:High Mobility Group Proteins / Q000235:genetics*; D051379:Mice; D016296:Mutagenesis; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014162:Transfection
D006609:High Mobility Group Proteins; D011993:Recombinant Fusion Proteins