The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The increased response rates in EZH2-mutant tumours mirrors preclinical studies and highlights the importance of understanding the mechanisms underlying EZH2 dependence”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [167]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Molecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551
Nishimura, R., Osako, T., Nishiyama, Y., Tashima, R., Nakano, M., Fujisue, M., Toyozumi, Y., & Arima, N. (2013) · Oncology · doi:10.1159/000353099 · Cited by 13,239
Sørlie, T., Perou, C. M., Tibshirani, R. J., Aas, T., Geisler, S. B., Johnsen, H., Hastie, T. J., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191367098 · Cited by 11,506
Gene expression profiling predicts clinical outcome of breast cancer
van 't Veer, L. J., Dai, H., van de Vijver, M. J., He, Y. D., Hart, A. A. M., Mao, M., Peterse, H. L., van der Kooy, K., Marton, M. J., Witteveen, A. T., et al. (2002) · Nature · doi:10.1038/415530a · Cited by 9,536
Ki67 expression in breast cancer
Elkablawy, M. A., Albasri, A. M., Mohammed, R. A., Hussainy, A. S., Nouh, M. M., & Alhujaily, A. S. (2016) · Saudi Medical Journal · doi:10.15537/smj.2016.2.12285 · Cited by 4,382
Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S., & Zhang, Y. (2002) · Science · doi:10.1126/science.1076997 · Cited by 3,775
Jemal, A., Murray, T., Samuels, A., Ghafoor, A., Ward, E., & Thun, M. J. (2003) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.53.1.5 · Cited by 3,275
The polycomb group protein EZH2 is involved in progression of prostate cancer
Varambally, S., Dhanasekaran, S. M., Zhou, M., Barrette, T. R., Kumar-Sinha, C., Sanda, M. G., Ghosh, D., Pienta, K. J., Sewalt, R. G. A. B., Otte, A. P., et al. (2002) · Nature · doi:10.1038/nature01075 · Cited by 2,717
Self-citationHaagenson, C. (1971) · Cited by 1,773
Gene-Expression Profiles in Hereditary Breast Cancer
Hedenfalk, I. A., Duggan, D. J., Chen, Y., Radmacher, M. D., Bittner, M. L., Simon, R., Meltzer, P. S., Gusterson, B. A., Esteller, M., Raffeld, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200102223440801 · Cited by 1,732
Delineation of prognostic biomarkers in prostate cancer
Dhanasekaran, S. M., Barrette, T. R., Ghosh, D., Shah, R. B., Varambally, S., Kurachi, K., Pienta, K. J., Rubin, M. A., & Chinnaiyan, A. M. (2001) · Nature · doi:10.1038/35090585 · Cited by 1,675
Self-citationJacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
Histone Methyltransferase Activity of a Drosophila Polycomb Group Repressor Complex
Müller, J., Hart, C. M., Francis, N. J., Vargas, M. L., Sengupta, A. K., Wild, B., Miller, E., O’Connor, M. B., Kingston, R. E., & Simon, J. A. (2002) · Cell · doi:10.1016/s0092-8674(02)00976-5 · Cited by 1,553
Czermin, B., Melfi, R., McCabe, D., Seitz, V., Imhof, A., & Pirrotta, V. (2002) · Cell · doi:10.1016/s0092-8674(02)00975-3 · Cited by 1,536
Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARFPreprint
Jacobs, J. J. L., Scheijen, B., Voncken, J. W., Kieboom, K., Berns, A. J. M., & van Lohuizen, M. (1999) · Genes & Development · doi:10.1101/gad.13.20.2678 · Cited by 1,069
Stabilization of Chromatin Structure by PRC1, a Polycomb Complex
Shao, Z., Raible, F., Mollaaghababa, R., Guyon, J. R., Wu, C.-T., Bender, W. W., & Kingston, R. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80604-2 · Cited by 821
Validation of Tissue Microarray Technology in Breast Carcinoma
Camp, R. L., Charette, L. A., & Rimm, D. L. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780204 · Cited by 811
Gruvberger-Saal, S. K., Ringnér, M., Chen, Y., Panavally, S., Saal, L. H., Borg, Å., Fernö, M., Peterson, C., & Meltzer, P. S. (2001) · PubMed · Cited by 677
Rhodes, D. R., Barrette, T. R., Rubin, M. A., Ghosh, D., & Chinnaiyan, A. M. (2002) · PubMed · Cited by 656
Self-citationvan der Vlag, J., & Otte, A. P. (1999) · Nature Genetics · doi:10.1038/70602 · Cited by 527
Self-citationZhou, M., Chinnaiyan, A. M., Kleer, C. G., Lucas, P. C., & Rubin, M. A. (2002) · The American Journal of Surgical Pathology · doi:10.1097/00000478-200207000-00012 · Cited by 296
Self-citationLaible, G., Wolf, A., Dorn, R., Reuter, G., Nislow, C., Lebersorger, A., Popkin, D., Pillus, L., & Jenuwein, T. (1997) · The EMBO Journal · doi:10.1093/emboj/16.11.3219 · Cited by 279
Tie, F., Furuyama, T., Prasad-Sinha, J., Jane, E. P., & Harte, P. J. (2001) · Development · doi:10.1242/dev.128.2.275 · Cited by 272
Sewalt, R. G. A. B., van der Vlag, J., Gunster, M. J., Hamer, K. M., den Blaauwen, J. L., Satijn, D. P. E., Hendrix, T., DRIEL, R. V., & Otte, A. P. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3586 · Cited by 221
Self-citationPrognostic Factors in Breast Cancer: Current and New Predictors of Metastasis
Hayes, D. F., Isaacs, C. J., & Stearns, V. (2001) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1014778713034 · Cited by 207
Self-citationHayes, D. F., Trock, B. J., & Harris, A. L. (1998) · Breast Cancer Research and Treatment · doi:10.1023/a:1006197805041 · Cited by 189
Self-citationCoexpression of BMI-1 and EZH2 Polycomb Group Genes in Reed-Sternberg Cells of Hodgkin’s Disease
Raaphorst, F. M., van Kemenade, F. J., Blokzijl, T., Fieret, E. J. H., Hamer, K. M., Satijn, D. P. E., Otte, A. P., & Meijer, C. J. L. M. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64583-x · Cited by 171
Self-citationSuberoylanilide Hydroxamic Acid as a Potential Therapeutic Agent for Human Breast Cancer Treatment
Huang, L., & Pardee, A. B. (2000) · Molecular Medicine · doi:10.1007/bf03401823 · Cited by 164
Morris, V. L., Koop, S., MacDonald, I. C., Schmidt, E. E., Grattan, M., Percy, D. H., Chambers, A. F., & Groom, A. C. (1994) · Clinical & Experimental Metastasis · doi:10.1007/bf01755879 · Cited by 133
Livant, D. L., Brabec, R. K., Pienta, K. J., Allen, D. L., Kurachi, K., Markwart, S. M., & Upadhyaya, A. (2000) · PubMed · Cited by 116
Self-citationPolycomb group protein complexes: do different complexes regulate distinct target genes?
Satijn, D. P. E., & Otte, A. P. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00130-x · Cited by 115
Self-citationSewalt, R. G. A. B., Lachner, M., Vargas, M., Hamer, K. M., den Blaauwen, J. L., Hendrix, T., Melcher, M., Schweizer, D., Jenuwein, T., & Otte, A. P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5539-5553.2002 · Cited by 91
Self-citationPerrone, E. E. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.11.937 · Cited by 83
erbB-2 Overexpression in Human Mammary Epithelial Cells Confers Growth Factor Independence
Ignatoski, K. M. W., LaPointe, A. J., Radany, E. H., & Ethier, S. P. (1999) · Endocrinology · doi:10.1210/endo.140.8.6939 · Cited by 57
Do we need prognostic factors in nodal-negative breast cancer?
Hayes, D. F. (2000) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00303-2 · Cited by 39
Self-citationLivant, D. L., Linn, S., Markwart, S. M., & Shuster, J. (1995) · PubMed · Cited by 32
Self-citation
Flagged first, then by citations
1 of the 38 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
- Ellis M. Hayes D. & Lippman M. (2000) in Diseases of the Breast eds. Harris J. Lippman M. E. & Morrow M. (Lippincott–Raven Philadelpha) pp. 749–798.
- Clark G. M. (1996) in Diseases of the Breast eds. Harris. J. L. M.. Morrow M. & Hellman S. (Lippincott–Raven Philadephia) pp. 461–485.
- Tie, F., Furuyama, T., Prasad-Sinha, J., Jane, E. & Harte, P. J. (2001) Development (Cambridge, U.K.) 128, 275–286.
- Livant, D. L., Linn, S., Markwart, S. & Shuster, J. (1995) Cancer Res. 55, 5085–5093.7585556
- Rhodes, D. R., Barrette, T. R., Rubin, M. A., Ghosh, D. & Chinnaiyan, A. M. (2002) Cancer Res. 62, 4427–4433.12154050
- Gruvberger, S., Ringner, M., Chen, Y., Panavally, S., Saal, L. H., Borg, A., Ferno, M., Peterson, C. & Meltzer, P. S. (2001) Cancer Res. 61, 5979–5984.11507038
- Livant, D. L., Brabec, R. K., Pienta, K. J., Allen, D. L., Kurachi, K., Markwart, S. & Upadhyaya, A. (2000) Cancer Res. 60, 309–320.10667582
Cited by
Sorted by citations
Regulation of chromatin by histone modifications
Bannister, A. J., & Kouzarides, T. (2011) · Cell Research · doi:10.1038/cr.2011.22 · Cited by 6,012
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
Gupta, R. A., Shah, N., Wang, K., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M.-C., Hung, T., Argani, P., Rinn, J. L., et al. (2010) · Nature · doi:10.1038/nature08975 · Cited by 5,205
Ginestier, C., Hur, M. H., Charafe‐Jauffret, E., Monville, F., Dutcher, J. A., Brown, M., Jacquemier, J. D., Viens, P., Kleer, C. G., Liu, S., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.08.014 · Cited by 4,093
Self-citationThe Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347
Metastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2622 · Cited by 2,716
Metadata
- Authors
- 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.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-09-19
- Volume
- 100
- Issue
- 20
- Pages
- 11606-11611
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC208805
- OpenAlex
- W2100365251
- Cited by
- 1,649
- References
- 38
- Citations by year
- 2026: 21 · 2025: 43 · 2024: 53 · 2023: 72 · 2022: 55 · 2021: 67 · 2020: 94 · 2019: 69 · 2018: 83 · 2017: 91 · 2016: 109 · 2015: 109 · 2014: 116 · 2013: 114 · 2012: 108
- FWCI
- 12.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Cancer Institute (P50-CA-69568, R01CA097063, R01 CA97063, P50CA069568)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- EZH2, Polycomb group proteins, breast cancer aggressiveness, breast cancer progression, cell invasion, anchorage-independent growth, oncogenic transformation, mammary epithelial cells, SET domain, histone deacetylase activity, transcriptional repression, cellular memory, prognostic factors
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Breast, Breast Neoplasms, Cell Transformation, Neoplastic, DNA-Binding Proteins, Epithelial Cells, Female, Humans, Immunohistochemistry, Proteins, RNA, Messenger, Transcription Factors, Polymerase Chain Reaction, Polycomb Repressive Complex 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
