Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2.
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.
Pentimalli
Francesca
F
Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, 80131 Naples, Italy.
Dentice
Monica
M
Fedele
Monica
M
Pierantoni
Giovanna Maria
GM
Cito
Letizia
L
Pallante
Pierlorenzo
P
Santoro
Massimo
M
Viglietto
Giuseppe
G
Dal Cin
Paola
P
Fusco
Alfredo
A
D000260:Adenoviruses, Human / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D016373:DNA, Antisense / Q000008:administration & dosage / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D025743:HMGA2 Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D025743:HMGA2 Protein