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ESR1 gene amplification: another mechanism regulating the cellular levels of ERα

Nature Reviews Cancer volume 11, page 823 (2011)Cite this article

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We read with great interest the Review (The different roles of ER subtypes in cancer biology and therapy. Nature Rev. Cancer 11, 597–608 (2011))1 by Thomas and Gustafsson, in which the authors addressed the mechanisms of action and regulation of oestrogen receptors (ERs), the distinct biological effect of ER isoforms, and the roles of ERs in cancer prognosis and targeted therapies. Regarding the regulation of cellular levels of ERs, the authors systemically stated the potential mechanisms, including promoter methylation, post-transcriptional regulation by specific microRNAs and proteasome-mediated degradation of ER proteins. Although the aforementioned mechanisms are the main pathways of ER regulation, the complete mechanisms of ER upregulation are still not fully understood. One mechanism that may lead to the overexpression of a given gene in neoplastic cells is gene amplification, and ESR1 gene amplification has been observed in some cancer cells2. We believe that this issue, which is not mentioned in the Review, deserves to be discussed when illustrating the mechanisms of upregulation of ERα.

It has recently been reported that expression of ERα, but not expression of ERβ, is driven in some cases by ESR1 amplification2. Holst et al. used tissue microarray analysis of more than 2,000 samples to demonstrate that 20.6% of breast cancers contained ESR1 amplification2; Burkhardt et al. showed that amplification rates of ESR1 in ductal carcinoma in situ (DCIS), DCIS with invasive cancer and the invasive component did not differ significantly from one another, with rates of 19.0%, 24.1% and 21.3%, respectively3. More interestingly, almost all tumours with ESR1 amplification showed ERα protein overexpression2. It is therefore not surprising that ESR1 amplification in breast cancers was found to be associated with improved survival in women who had received adjuvant tamoxifen. In patients with ER-positive disease who received tamoxifen monotherapy, survival was indeed shown to be longer in patients who had ESR1 amplification than in patients who did not have ESR1 amplification2. Another Japanese report also showed that ESR1 amplification, which was found in 22.6% of samples by three-dimensional fluorescence in situ hybridization (FISH) assay, strongly correlates with higher expression levels of ERα, and that patients with ESR1 amplification in tumours apparently experience longer disease-free survival than those without ESR1 amplification4. These observations consistently suggest that ESR1 amplification is helpful in selecting patients who may potentially benefit from endocrine therapy. Besides breast cancer, ESR1 amplification occurs in more than 20% of endometrial carcinomas (established using FISH5) but it rarely occurs (2%) in ovarian cancer6.

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References

  1. Thomas, C. & Gustafsson, J. A. The different roles of ER subtypes in cancer biology and therapy. Nature Rev. Cancer 11, 597–608 (2011).

    Article  CAS  Google Scholar 

  2. Holst, F. et al. Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nature Genet. 39, 655–660 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Burkhardt, L. et al. Gene amplification in ductal carcinoma in situ of the breast. Breast Cancer Res. Treat 123, 757–765 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Tomita, S. et al. Estrogen receptor alpha gene ESR1 amplification may predict endocrine therapy responsiveness in breast cancer patients. Cancer Sci. 100, 1012–1017 (2009).

    Article  CAS  PubMed  Google Scholar 

  5. Lebeau, A. et al. Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions. J. Pathol. 216, 151–157 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Issa, R. M. et al. Estrogen receptor gene amplification occurs rarely in ovarian cancer. Mod. Pathol. 22, 191–196 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Brown, L. A. et al. ESR1 gene amplification in breast cancer: a common phenomenon? Nature Genet. 40, 806–812 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Horlings, H. M. et al. ESR1 gene amplification in breast cancer: a common phenomenon? Nature Genet. 40, 807–812 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Reis-Filho, J. S. et al. ESR1 gene amplification in breast cancer: a common phenomenon? Nature Genet. 40, 809–812 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Vincent-Salomon, A., Raynal, V., Lucchesi, C., Gruel, N. & Delattre, O. ESR1 gene amplification in breast cancer: a common phenomenon? Nature Genet. 40, 809; author reply 810–812 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Holst, F. et al. ESR1 gene amplification in breast cancer: a common phenomenon? Reply. Nature Genet. 40, 810–812 (2008).

    Article  CAS  Google Scholar 

  12. Chin, S. F. et al. Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers. Oncogene 26, 1959–1970 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Nessling, M. et al. Candidate genes in breast cancer revealed by microarray-based comparative genomic hybridization of archived tissue. Cancer Res. 65, 439–447 (2005).

    CAS  PubMed  Google Scholar 

  14. Adelaide, J. et al. Absence of ESR1 amplification in a series of breast cancers. Int. J. Cancer 123, 2970–2972 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. Moelans, C. B., de Weger, R. A., Monsuur, H. N., Vijzelaar, R. & van Diest, P. J. Molecular profiling of invasive breast cancer by multiplex ligation-dependent probe amplification-based copy number analysis of tumor suppressor and oncogenes. Mod. Pathol. 23, 1029–1039 (2010).

    Article  CAS  PubMed  Google Scholar 

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  1. Ke-Da Yu and Zhi-Ming Shao are at the Department of Breast Surgery, and the Department of Oncology, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai 200032, China, as well as at the Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.,

    Ke-Da Yu & Zhi-Ming Shao

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Correspondence to Zhi-Ming Shao.

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Yu, KD., Shao, ZM. ESR1 gene amplification: another mechanism regulating the cellular levels of ERα. Nat Rev Cancer 11, 823 (2011). https://doi.org/10.1038/nrc3093-c1

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