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Int. J. Mol. Sci. 2019, 20(8), 1881; https://doi.org/10.3390/ijms20081881

Clinical and Biological Significance of ESR1 Gene Alteration and Estrogen Receptors Isoforms Expression in Breast Cancer Patients

1
Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-211 Gdansk, Poland
2
Department of Pathology, Medical University of Gdansk, 80-210 Gdansk, Poland
3
Department of Biology and Genetics, Medical University of Gdansk, 80-211 Gdansk, Poland
4
Department of Surgical Oncology, Medical University of Gdansk, 80-211 Gdansk, Poland
5
Department of Oncology and Radiotherapy, Medical University of Gdansk, 80-210 Gdansk, Poland
6
Department of Medical Laboratory Diagnostics -Biobank, Medical University of Gdansk, Gdansk, 80-210 Gdansk, Poland
7
Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.PL), 80-210 Gdansk, Poland
*
Author to whom correspondence should be addressed.
Received: 6 February 2019 / Revised: 11 April 2019 / Accepted: 12 April 2019 / Published: 16 April 2019
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Abstract

The amplification of estrogen receptor alpha (ERα) encoded by the ESR1 gene has been described as having a prognostic role in breast cancer patients. However, increased dosage of the ESR1 gene (tested by real-time PCR) is also observed in ER-negative breast cancers, which might suggest the expression of alternative isoforms of ERα (other than classical ERα of 66 kDa). In the current work, we have investigated the ESR1 gene dosage in 402 primary breast cancer patients as well as the expression of ERα isoforms—ERα66 and ERα36—on mRNA and protein levels. The obtained results were correlated with clinicopathological data of the patients. Results showed that increased ESR1 gene dosage is not related to ESR1 gene amplification measured by fluorescent in situ hybridization (FISH), but it correlates with the decreased expression of ERα66 isoform (p = 0.01). Interestingly, the short ER isoform ERα36 was expressed in samples with increased ESR1 gene dosage, suggesting that genomic aberration might influence the expression of that particular isoform. Similarly to ESR1 increased gene dosage, high ERα36 expression was linked with the decreased disease-free survival of the patients (p = 0.05), which was independent of the status of the classical ERα66 level in breast tumors. View Full-Text
Keywords: breast cancer; estrogen receptor; ERα36, ERα66, gene amplification; prognostic factor breast cancer; estrogen receptor; ERα36, ERα66, gene amplification; prognostic factor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Nagel, A.; Szade, J.; Iliszko, M.; Elzanowska, J.; Welnicka-Jaskiewicz, M.; Skokowski, J.; Stasilojc, G.; Bigda, J.; Sadej, R.; Zaczek, A.; Markiewicz, A. Clinical and Biological Significance of ESR1 Gene Alteration and Estrogen Receptors Isoforms Expression in Breast Cancer Patients. Int. J. Mol. Sci. 2019, 20, 1881.

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