A truncated HMGA1 gene induces proliferation of the 3T3-L1 pre-adipocytic cells: a model of human lipomas.
The high mobility group A (HMGA) proteins are non-histone chromosomal proteins implicated in the organization of chromatin structure and in the assembly of protein complexes on the promoters of several inducible genes. Rearrangements of HMGA1 and HMGA2 genes, consequent to chromosomal translocation, have been frequently detected in human benign tumours of mesenchymal origin including lipomas. We have demonstrated previously that 3T3-L1 adipocytic differentiation is associated with increased HMGA1 protein levels, and that the block of HMGA1 synthesis dramatically increases the growth rate of 3T3-L1 cells and suppresses adipocytic differentiation. Here we have examined the role of a truncated HMGA1 gene in adipocytic cell growth. We have found that expression of the truncated Hmga1 gene (Hmga1/T) dramatically increases 3T3-L1 cell growth without blocking adipocytic differentiation. The Hmga1/T 3T3-L1 cells had higher E2F activity than the wild-type cells, and a deregulated cell cycle. In fact, the Hmga1/T cells had a reduced G0/G1 fraction, and a greater number of cells in S-phase. However, consistent with the benign nature of tumours associated with HMGA1 rearrangements, the Hmga1/T 3T3-L1 cells did not acquire the malignant phenotype. These results suggest a critical role played by HMGA1 rearrangements in the generation of human lipomas.
Pierantoni
Giovanna Maria
GM
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli 'Federico II', via Pansini 5, I-80131 Naples, Italy.
Battista
Sabrina
S
Pentimalli
Francesca
F
Fedele
Monica
M
Visone
Rosa
R
Federico
Antonella
A
Santoro
Massimo
M
Viglietto
Giuseppe
G
Fusco
Alfredo
A
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002875:Chromosomes / Q000648:ultrastructure; D005434:Flow Cytometry; D016193:G1 Phase; D005822:Genetic Vectors; D025741:HMGA1a Protein / Q000235:genetics*; D015151:Immunoblotting; D008067:Lipoma / Q000378:metabolism; D051379:Mice; D008858:Microscopy, Phase-Contrast; D008957:Models, Genetic; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016192:Resting Phase, Cell Cycle; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D025741:HMGA1a Protein