Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect

Michael Milyavsky; Igor Shats; Alina Cholostoy; Ran Brosh; Yosef Buganim; Lilach Weisz; Ira Kogan; Merav Cohen; Maria Shatz; Shalom Madar; Eyal Kalo; Naomi Goldfinger; Jun Yuan; Shulamit Ron; Karen MacKenzie; Amir Eden; Varda Rotter

doi:10.1016/j.ccr.2006.11.022

Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect

Michael Milyavsky, Igor Shats, Alina Cholostoy, Ran Brosh, Yosef Buganim, Lilach Weisz, Ira Kogan, Merav Cohen, Maria Shatz, Shalom Madar, Eyal Kalo, Naomi Goldfinger, Jun Yuan, Shulamit Ron, Karen MacKenzie, Amir Eden, Varda Rotter^*

^*Corresponding author for this work

Department of Cell and Developmental Biology

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

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 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.

Original language	English
Pages (from-to)	133-146
Number of pages	14
Journal	Cancer Cell
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2006.11.022
State	Published - 13 Feb 2007

Bibliographical note

Funding Information:
The authors would like to thank Dr. Dina Ron for her helpful advice on in situ hybridization analysis. This research was supported by a Center of Excellence Grant from the Flight Attendant Medical Research Institute (FAMRI) and the Yad Abraham Center for Cancer Diagnosis and Therapy. V.R. is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann Institute of Science.

Keywords

CELLCYCLE

UN SDGs

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10.1016/j.ccr.2006.11.022

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Milyavsky, M., Shats, I., Cholostoy, A., Brosh, R., Buganim, Y., Weisz, L., Kogan, I., Cohen, M., Shatz, M., Madar, S., Kalo, E., Goldfinger, N., Yuan, J., Ron, S., MacKenzie, K., Eden, A., & Rotter, V. (2007). Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect. Cancer Cell, 11(2), 133-146. https://doi.org/10.1016/j.ccr.2006.11.022

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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 TGFβ required for TGFβ-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.",

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Milyavsky, M, Shats, I, Cholostoy, A, Brosh, R, Buganim, Y, Weisz, L, Kogan, I, Cohen, M, Shatz, M, Madar, S, Kalo, E, Goldfinger, N, Yuan, J, Ron, S, MacKenzie, K, Eden, A & Rotter, V 2007, 'Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect', Cancer Cell, vol. 11, no. 2, pp. 133-146. https://doi.org/10.1016/j.ccr.2006.11.022

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AU - Milyavsky, Michael

AU - Shats, Igor

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AU - Buganim, Yosef

AU - Weisz, Lilach

AU - Kogan, Ira

AU - Cohen, Merav

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AU - Madar, Shalom

AU - Kalo, Eyal

AU - Goldfinger, Naomi

AU - Yuan, Jun

AU - Ron, Shulamit

AU - MacKenzie, Karen

AU - Eden, Amir

AU - Rotter, Varda

N1 - Funding Information: The authors would like to thank Dr. Dina Ron for her helpful advice on in situ hybridization analysis. This research was supported by a Center of Excellence Grant from the Flight Attendant Medical Research Institute (FAMRI) and the Yad Abraham Center for Cancer Diagnosis and Therapy. V.R. is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann Institute of Science.

PY - 2007/2/13

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Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect

Abstract

Bibliographical note

Keywords

UN SDGs

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