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

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
Externally published	Yes

Funding

Funders	Funder number
Yad Abraham Center for Cancer Diagnosis and Therapy
Flight Attendant Medical Research Institute

Keywords

CELLCYCLE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ccr.2006.11.022

Cite this

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

@article{2179dfddc7854b80b0e29e3b3437e0ff,

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 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.",

keywords = "CELLCYCLE",

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

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. ",

year = "2007",

month = feb,

day = "13",

doi = "10.1016/j.ccr.2006.11.022",

language = "אנגלית",

volume = "11",

pages = "133--146",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "2",

}

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

TY - JOUR

T1 - Inactivation of Myocardin and p16 during Malignant Transformation Contributes to a Differentiation Defect

AU - Milyavsky, Michael

AU - Shats, Igor

AU - Cholostoy, Alina

AU - Brosh, Ran

AU - Buganim, Yosef

AU - Weisz, Lilach

AU - Kogan, Ira

AU - Cohen, Merav

AU - Shatz, Maria

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

Y1 - 2007/2/13

N2 - 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.

AB - 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.

KW - CELLCYCLE

UR - http://www.scopus.com/inward/record.url?scp=33846804362&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2006.11.022

DO - 10.1016/j.ccr.2006.11.022

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 17292825

AN - SCOPUS:33846804362

SN - 1535-6108

VL - 11

SP - 133

EP - 146

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

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

Abstract

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this