TRUNCATED AND CHIMERIC HMGI-C GENES INDUCE NEOPLASTIC TRANSFORMATION OF NIH3T3 MURINE FIBROBLASTS

Overexpression of the high mobility group I (HMGI) proteins is often a ssociated with the malignant phenotype. Moreover, many benign human tu mors, mainly of mesenchymal origin, are characterized by rearrangement s 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 tru ncated form of HMGI-C protein carrying only the three DNA-binding doma ins, 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 unrearra nged wildtype HMGI-C cDNA did not exert any transforming activity. The se findings indicate that rearranged forms of HMGI-C play a role in ce ll transformation.