Inactivation of myocardin and p16 during malignant transformation contributes to a differentiation defect
Autor: | Merav Cohen, Jun Yuan, Maria Shatz, Yosef Buganim, Michael Milyavsky, Eyal Kalo, Shalom Madar, Shulamit Ron, Ran Brosh, Naomi Goldfinger, Varda Rotter, Alina Cholostoy, Lilach Weisz, Igor Shats, Karen L. MacKenzie, Ira Kogan, Amir Eden |
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Rok vydání: | 2006 |
Předmět: |
Cancer Research
Blotting Western Fluorescent Antibody Technique CELLCYCLE Biology Malignant transformation Colony-Forming Units Assay Mesoderm Transforming Growth Factor beta Neoplasms medicine Transcriptional regulation Cell Adhesion Humans RNA Small Interfering Promoter Regions Genetic Lung Cells Cultured Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation Cardiac muscle Contact inhibition Nuclear Proteins Cell Differentiation Cell Biology Cell cycle DNA Methylation Fibroblasts medicine.disease Malignant Growth Cell biology medicine.anatomical_structure Cell Transformation Neoplastic Oncology Gene Expression Regulation Myocardin Immunology embryonic structures cardiovascular system Trans-Activators Sarcoma Plasmids |
Zdroj: | Cancer cell. 11(2) |
ISSN: | 1535-6108 |
Popis: | Summary 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 TGFβ required for TGFβ-mediated differentiation of human fibroblasts. Serum deprivation, intact contact inhibition response, and the p16 ink4a /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. |
Databáze: | OpenAIRE |
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