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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.<\/jats:p>","DOI":"10.1073\/pnas.1933744100","type":"journal-article","created":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T19:44:34Z","timestamp":1065037474000},"page":"11606-11611","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1384,"title":["EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells"],"prefix":"10.1073","volume":"100","author":[{"given":"Celina G.","family":"Kleer","sequence":"first","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Qi","family":"Cao","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Sooryanarayana","family":"Varambally","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Ronglai","family":"Shen","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Ichiro","family":"Ota","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Scott A.","family":"Tomlins","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Debashis","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Biostatistics, Internal Medicine, Surgery, Radiation Oncology, and Urology, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; Swammerdam Institute for Life Sciences, Biocentrum Amsterdam, University of Amsterdam, 1018 TV Amsterdam, The Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"given":"Richard G. 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