EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

Celina G. Kleer; Qi Cao; Sooryanarayana Varambally; Ronglai Shen; Ichiro Ota; Scott A. Tomlins; Debashis Ghosh; Richard G.A.B. Sewalt; Arie P. Otte; Daniel F. Hayes; Michael S. Sabel; Donna Livant; Stephen J. Weiss; Mark A. Rubin; Arul M. Chinnaiyan

doi:10.1073/pnas.1933744100

EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

Celina G. Kleer, Qi Cao, Sooryanarayana Varambally, Ronglai Shen, Ichiro Ota, Scott A. Tomlins, Debashis Ghosh, Richard G.A.B. Sewalt, Arie P. Otte, Daniel F. Hayes, Michael S. Sabel, Donna Livant, Stephen J. Weiss, Mark A. Rubin, Arul M. Chinnaiyan

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1435 Scopus citations

Abstract

The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.

Original language	English (US)
Pages (from-to)	11606-11611
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	20
DOIs	https://doi.org/10.1073/pnas.1933744100
State	Published - Sep 30 2003

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Kleer, C. G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S. A., Ghosh, D., Sewalt, R. G. A. B., Otte, A. P., Hayes, D. F., Sabel, M. S., Livant, D., Weiss, S. J., Rubin, M. A., & Chinnaiyan, A. M. (2003). EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 100(20), 11606-11611. https://doi.org/10.1073/pnas.1933744100

EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. / Kleer, Celina G.; Cao, Qi; Varambally, Sooryanarayana et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 20, 30.09.2003, p. 11606-11611.

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

Kleer, CG, Cao, Q, Varambally, S, Shen, R, Ota, I, Tomlins, SA, Ghosh, D, Sewalt, RGAB, Otte, AP, Hayes, DF, Sabel, MS, Livant, D, Weiss, SJ, Rubin, MA & Chinnaiyan, AM 2003, 'EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 20, pp. 11606-11611. https://doi.org/10.1073/pnas.1933744100

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abstract = "The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.",

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AU - Kleer, Celina G.

AU - Cao, Qi

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AU - Shen, Ronglai

AU - Ota, Ichiro

AU - Tomlins, Scott A.

AU - Ghosh, Debashis

AU - Sewalt, Richard G.A.B.

AU - Otte, Arie P.

AU - Hayes, Daniel F.

AU - Sabel, Michael S.

AU - Livant, Donna

AU - Weiss, Stephen J.

AU - Rubin, Mark A.

AU - Chinnaiyan, Arul M.

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AB - The Polycomb Group Protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive prostate cancer. Here we investigate the functional role of EZH2 in cancer cell invasion and breast cancer progression. EZH2 transcript and protein were consistently elevated in invasive breast carcinoma compared with normal breast epithelia. Tissue microarray analysis, which included 917 samples from 280 patients, demonstrated that EZH2 protein levels were strongly associated with breast cancer aggressiveness. Overexpression of EZH2 in immortalized human mammary epithelial cell lines promotes anchorage-independent growth and cell invasion. EZH2-mediated cell invasion required an intact SET domain and histone deacetylase activity. This study provides compelling evidence for a functional link between dysregulated cellular memory, transcriptional repression, and neoplastic transformation.

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EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells

Abstract

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