The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Regulation of ERBB2 by oestrogen receptor–PAX2 determines response to tamoxifen
Open accessAbstract
Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug response, yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen–ER and tamoxifen–ER complexes directly repress ERBB2 transcription by means of a cis-regulatory element within the ERBB2 gene in human cell lines. We implicate the paired box 2 gene product (PAX2), in a previously unrecognized role, as a crucial mediator of ER repression of ERBB2 by the anti-cancer drug tamoxifen. We show that PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transcription, the outcome of which determines tamoxifen response in breast cancer cells. The repression of ERBB2 by ER-PAX2 links these two breast cancer subtypes and suggests that aggressive ERBB2-positive tumours can originate from ER-positive luminal tumours by circumventing this repressive mechanism. These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer.
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Cites
Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer
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Self-citationGenome-wide analysis of estrogen receptor binding sites
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FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription
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Cited by
Biological determinants of endocrine resistance in breast cancer
Musgrove, E. A., & Sutherland, R. L. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2713 · Cited by 1,252
The different roles of ER subtypes in cancer biology and therapy
Thomas, C., & Gustafsson, J.-Å. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3093 · Cited by 654
Klann, T. S., Black, J. B., Chellappan, M., Safi, A., Song, L., Hilton, I. B., Crawford, G. E., Reddy, T. E., & Gersbach, C. A. (2017) · Nature Biotechnology · doi:10.1038/nbt.3853 · Cited by 447
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Day, F. R., Hinds, D. A., Tung, J. Y., Stolk, L., Styrkarsdottir, U., Saxena, R., Bjonnes, A., Broer, L., Dunger, D. B., Halldorsson, B. V., et al. (2015) · Nature Communications · doi:10.1038/ncomms9464 · Cited by 459
Metadata
- Authors
- Hurtado, A., Holmes, K. A., Geistlinger, T. R., Hutcheson, I. R., Nicholson, R. I., Brown, M., Jiang, J., Howat, W. J., Ali, S., & Carroll, J. S.
- Venue
- Nature
- Published
- 2008-12-01
- Volume
- 456
- Issue
- 7222
- Pages
- 663-666
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1998162919
- Cited by
- 321
- References
- 29
- FWCI
- 18.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hurtado, A., Holmes, K. A., Geistlinger, T. R., Hutcheson, I. R., Nicholson, R. I., Brown, M., Jiang, J., Howat, W. J., Ali, S., & Carroll, J. S. (2008). Regulation of ERBB2 by oestrogen receptor–PAX2 determines response to tamoxifen. Nature. https://doi.org/10.1038/nature07483
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
