Atypical lipomatous tumors (ALTs)/well-differentiated liposarcomas represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic proliferation. These tumors are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes that contain several copies of the chromosomal region 12q13-15, in which the HMGA2 gene is located. Deregulation of the HMGA2 gene is a common molecular alteration implicated in the development of a variety of benign tumors, such as lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. In this study, we observed HMGA2 overexpression in 7 of 12 ALT primary cell cultures examined. Subsequently, we generated an adenovirus containing the HMGA2 gene in the antisense orientation (Ad-A2as) to study the effect of HMGA2 protein suppression in ALT cells. The infection of six ALT cells, three of which were positive for HMGA2 expression, resulted in growth inhibition coupled with a significant increase in apoptosis. In addition, the growth of the ALT cells negative for HMGA2 expression was not affected by the infection with either the Ad-A2as or the control virus. On the basis of these findings, the targeting of the HMGA2 protein expression may represent a promising approach for treating the well-differentiated liposarcomas resistant to conventional therapies.

Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2

Pentimalli F;
2003

Abstract

Atypical lipomatous tumors (ALTs)/well-differentiated liposarcomas represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic proliferation. These tumors are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes that contain several copies of the chromosomal region 12q13-15, in which the HMGA2 gene is located. Deregulation of the HMGA2 gene is a common molecular alteration implicated in the development of a variety of benign tumors, such as lipomas, uterine leiomyomas, and pulmonary chondroid hamartomas. In this study, we observed HMGA2 overexpression in 7 of 12 ALT primary cell cultures examined. Subsequently, we generated an adenovirus containing the HMGA2 gene in the antisense orientation (Ad-A2as) to study the effect of HMGA2 protein suppression in ALT cells. The infection of six ALT cells, three of which were positive for HMGA2 expression, resulted in growth inhibition coupled with a significant increase in apoptosis. In addition, the growth of the ALT cells negative for HMGA2 expression was not affected by the infection with either the Ad-A2as or the control virus. On the basis of these findings, the targeting of the HMGA2 protein expression may represent a promising approach for treating the well-differentiated liposarcomas resistant to conventional therapies.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.12572/8033
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