Strong Smooth Muscle Differentiation Is Dependent on Myocardin Gene Amplification in Most Human Retroperitoneal Leiomyosarcomas
- 15 March 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 69 (6), 2269-2278
- https://doi.org/10.1158/0008-5472.can-08-1443
Abstract
Myocardin (MYOCD), a serum response factor (SRF) transcriptional cofactor, is essential for cardiac and smooth muscle development and differentiation. We show here by array-based comparative genomic hybridization, fluorescence in situ hybridization, and expression analysis approaches that MYOCD gene is highly amplified and overexpressed in human retroperitoneal leiomyosarcomas (LMS), a very aggressive well-differentiated tumor. MYOCD inactivation by shRNA in a human LMS cell line with MYOCD locus amplification leads to a dramatic decrease of smooth muscle differentiation and strongly reduces cell migration. Moreover, forced MYOCD expression in three undifferentiated sarcoma cell lines and in one liposarcoma cell line confers a strong smooth muscle differentiation phenotype and increased migration abilities. Collectively, these results show that human retroperitoneal LMS differentiation is dependent on MYOCD amplification/overexpression, suggesting that in these well-differentiated LMS, differentiation could be a consequence of an acquired genomic alteration. In this hypothesis, these tumors would not necessarily derive from cells initially committed to smooth muscle differentiation. These data also provide new insights on the cellular origin of these sarcomas and on the complex connections between oncogenesis and differentiation in mesenchymal tumors.Keywords
Other Versions
This publication has 42 references indexed in Scilit:
- Human Thyroid Tumor Cell Lines Derived from Different Tumor Types Present a Common Dedifferentiated PhenotypeCancer Research, 2007
- Advances in salivary gland pathologyHistopathology, 2007
- Mesenchymal Stem Cell Features of Ewing TumorsCancer Cell, 2007
- JUN Oncogene Amplification and Overexpression Block Adipocytic Differentiation in Highly Aggressive SarcomasCancer Cell, 2007
- Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entityBreast Cancer Research, 2007
- The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesisGenes & Development, 2006
- LPP Expression During In Vitro Smooth Muscle Differentiation and Stent-Induced Vascular InjuryCirculation Research, 2006
- Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardinCardiovascular Research, 2005
- Control of smooth muscle development by the myocardin family of transcriptional coactivatorsCurrent Opinion in Genetics & Development, 2004
- Myocardin Is a Key Regulator of CArG-Dependent Transcription of Multiple Smooth Muscle Marker GenesCirculation Research, 2003