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

• Published in: International journal of molecular sciences 2019-04, Vol.20 (8), p.1881
• Main Authors: Nagel, Anna, Szade, Jolanta, Iliszko, Mariola, Elzanowska, Julia, Welnicka-Jaskiewicz, Marzena, Skokowski, Jaroslaw, Stasilojc, Grzegorz, Bigda, Jacek, Sadej, Rafal, Zaczek, Anna, Markiewicz, Aleksandra
• Format: Article
• Language: English
• Subjects: Apoptosis; Breast - pathology; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Line, Tumor; Change detection; Estrogen Receptor alpha - genetics; Estrogen receptors; Estrogens; Female; Gene amplification; Gene Dosage; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Isoforms; Localization; MAP kinase; Medical prognosis; Prognosis; Protein Isoforms - genetics; Proteins; Signal transduction; Transcription factors; Tumors; Up-Regulation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20081881

The amplification of estrogen receptor alpha (ERα) encoded by the gene has been described as having a prognostic role in breast cancer patients. However, increased dosage of the 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 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 gene dosage is not related to gene amplification measured by fluorescent in situ hybridization (FISH), but it correlates with the decreased expression of isoform ( = 0.01). Interestingly, the short ER isoform was expressed in samples with increased gene dosage, suggesting that genomic aberration might influence the expression of that particular isoform. Similarly to increased gene dosage, high expression was linked with the decreased disease-free survival of the patients ( = 0.05), which was independent of the status of the classical level in breast tumors.