Pierantoni Giovanna Maria, Battista Sabrina, Pentimalli Francesca, Fedele Monica, Visone Rosa, Federico Antonella, Santoro Massimo, Viglietto Giuseppe, Fusco Alfredo
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.
Carcinogenesis. 2003 Dec;24(12):1861-9. doi: 10.1093/carcin/bgg149. Epub 2003 Sep 11.
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.
高迁移率族A（HMGA）蛋白是非组蛋白染色体蛋白，与染色质结构的组织以及几种诱导型基因启动子上蛋白质复合物的组装有关。在包括脂肪瘤在内的人类间充质来源的良性肿瘤中，经常检测到由于染色体易位导致的HMGA1和HMGA2基因重排。我们之前已经证明，3T3-L1脂肪细胞分化与HMGA1蛋白水平升高有关，并且HMGA1合成的阻断会显著提高3T3-L1细胞的生长速率并抑制脂肪细胞分化。在这里，我们研究了截短的HMGA1基因在脂肪细胞生长中的作用。我们发现，截短的Hmga1基因（Hmga1/T）的表达显著增加3T3-L1细胞的生长，而不会阻断脂肪细胞分化。Hmga1/T 3T3-L1细胞的E2F活性高于野生型细胞，并且细胞周期失调。事实上，Hmga1/T细胞的G0/G1期比例降低，S期细胞数量更多。然而，与与HMGA1重排相关的肿瘤的良性性质一致，Hmga1/T 3T3-L1细胞没有获得恶性表型。这些结果表明HMGA1重排在人类脂肪瘤的发生中起关键作用。
