Abstract 4980: Myocardin functions as an effective inducer of growth arrest and differentiation in human leiomyosarcoma cells

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 8_Supplement; p. 4980
• Main Authors: Kimura, Yasunori, Morita, Tsuyoshi, Hayashi, Ken'ichiro, Miki, Tsuneharu, Sobue, Kenji
• Format: Journal Article
• Language: English
• Published: 15.04.2010
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-4980

Abstract Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. We noticed that the expression of myocardin was markedly downregulated in human uterine leiomyosarcoma cells. Restoration of myocardin expression induced the re-expression of smooth muscle marker proteins and the formation of well-developed actin fibers. A concomitant increase in the expression of a CDK inhibitor, p21, led to a significant slowing of cell proliferation, via p21's inhibition of the G1/S transition. A p21 promoter-reporter assay showed that myocardin markedly increased p21's promoter activity. Furthermore, a serum response factor (SRF)-binding cis-element CArG-box in the p21 promoter region was required for this myocardin effect. Chromatin immunoprecipitation and DNA-protein binding assays showed that myocardin indirectly bound to the CArG-box in the p21 promoter through an interaction with SRF. Furthermore, immunohistochemistry revealed that the levels of myocardin and p21 were both lower in leiomyosarcoma samples than in normal smooth muscle tissue. Taken together, our results indicate that the downregulation of myocardin expression facilitates cell-cycle progression via the reduction of p21 expression in human leimyosarcomas, and suggest that myocardin could be a useful therapeutic target for this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4980.