title: Inactivation of myocardin and p16 during malignant transformation contributes to a differentiation defect.
abstract: Myocardin is known as an important transcriptional regulator in smooth and cardiac muscle development. Here we found that myocardin is frequently repressed during human malignant transformation, contributing to a differentiation defect. We demonstrate that myocardin is a transcriptional target of TGFbeta required for TGFbeta-mediated differentiation of human fibroblasts. Serum deprivation, intact contact inhibition response, and the p16ink4a/Rb pathway contribute to myocardin induction and differentiation. Restoration of myocardin expression in sarcoma cells results in differentiation and inhibition of malignant growth, whereas inactivation of myocardin in normal fibroblasts increases their proliferative potential. Myocardin expression is reduced in multiple types of human tumors. Collectively, our results demonstrate that myocardin is an important suppressive modifier of the malignant transformation process.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Milyavsky
authors.forename: Igor
authors.initials: I
authors.lastname: Shats
authors.forename: Alina
authors.initials: A
authors.lastname: Cholostoy
authors.forename: Ran
authors.initials: R
authors.lastname: Brosh
authors.forename: Yosef
authors.initials: Y
authors.lastname: Buganim
authors.forename: Lilach
authors.initials: L
authors.lastname: Weisz
authors.forename: Ira
authors.initials: I
authors.lastname: Kogan
authors.forename: Merav
authors.initials: M
authors.lastname: Cohen
authors.forename: Maria
authors.initials: M
authors.lastname: Shatz
authors.forename: Shalom
authors.initials: S
authors.lastname: Madar
authors.forename: Eyal
authors.initials: E
authors.lastname: Kalo
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldfinger
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Shulamit
authors.initials: S
authors.lastname: Ron
authors.forename: Karen
authors.initials: K
authors.lastname: MacKenzie
authors.forename: Amir
authors.initials: A
authors.lastname: Eden
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000196:embryology; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000494:pharmacology; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000099251:Myocardin
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099251:Myocardin