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Link to original content: http://pubmed.ncbi.nlm.nih.gov/36118080/
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. 2022 Sep 8:2022:7833389.
doi: 10.1155/2022/7833389. eCollection 2022.

Role of Estrogen Receptor-Positive/Negative Ratios in Regulating Breast Cancer

Yanchu Li  1 , Hengli Zhang  2 , Tingting Jiang  1 , Ping Li  1
Affiliations

Role of Estrogen Receptor-Positive/Negative Ratios in Regulating Breast Cancer

Yanchu Li et al. Evid Based Complement Alternat Med. .

Abstract

The alpha estrogen receptor (ERα) contributes to breast cancer progression and recent guidelines define ER positivity as ≥1% stained cells, and a few tumor tissues show no ERα expression at all or are at 100%. Although ER and aromatase inhibitors are widely used to treat hormone receptor-positive (HR+) breast cancer, their effect on tumor activity at different ERα levels remains unclear. Therefore, we investigated the role of ERα+/ERα- ratios in determining the ERα level. We used ERα stably transfected and wild-type MDA-MB-231 cells (MDA-MB-231Trans-ER and MDA-MB-231WT, respectively) as represented ER+ and ER- cells, respectively, and MCF-7 cells were the positive control. MDA-MB-231Trans-ER and MDA-MB-231WT cells were mixed and cocultured at a ratio of 0%, 20%, 40%, 70%, and 100%. Migration and invasion functions at different cell ratios were evaluated in vitro using the Transwell and scratch test. In a xenograft mouse model, the polarization of the tumor-associated (M2) macrophage and the expression of breast cancer gene 1 (BRCA1), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-α were measured. The results showed that the cell invasion and migration were significantly higher at 40% and 70% than they were at other ratios. Additionally, in vivo, the 70% ERα+/ERα-ratio was a critical indicator of cell activity and cytokine expression. The highest M2 level and expression of VEGR, TNF-α, BRCA1, and HER2 were shown at a ratio of 70%. Moreover, the effects of ERα were not linear in breast cancer, indicating that the ERα status requires continuous monitoring during long-term endocrine treatment. These results indicate that during HR+ breast cancer treatment, the ERα+/ERα- ratio may be a useful predictor and should be evaluated further.

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Conflict of interest statement

The authors declare that they have conflicts of interest.

Figures

Figure 1
Figure 1
Confirmation of ERα transfection. (a) ERα stably transfected in MDA-MB-231 cell. pEGFP-C1-ERα expression was observed (green fluoresce) 48 h after transfection. (b) Western blot assay: ERα protein highly expressed in MDA-MB-231Trans−ER cells. (c) MTT assay. Compared to the MDA-MB-231WT cells, the proliferation ability of MDA-MB-231Trans−ER cells was significantly inhibited (P < 0.05) and was similar to that of MCF-7 cells.
Figure 2
Figure 2
ERα expression (red) in vitro and in vivo. (a) In vitro evaluation of ERα expression in cocultured MDA-MB-231Trans−ER (ERα+) and MDA-MB-231WT (ERα−) cells at different ratios and MCF-7 alone group. In the 100% ERα+/ERα− ratio group, ERα protein expression was as high as observed in MCF-7 cells. With decreasing ERα+/ERα− ratio, the expression of ERα protein also decreased gradually. At the 0% ERα+/ERα−ratio group, ERα protein did not express at all. (b) Analysis of ERα gene expression by RT-PCR at different ERα+/ERα− ratio groups in tumor tissue. ERα expression decreased proportionally with decrease in the ERα+/ERα−ratio.
Figure 3
Figure 3
Invasion and migration assay in vitro. (a) 1/2: The numbers of cells that crossed the Matrigel filter showed that cell invasion ability significantly stabilized at 40% and 70% ERα+/ERα−ratio. (b) 1/2: Compared to the MCF-7 group (control), in the 70% ERα+/ERα− ratio group, the most cells migrated rapidly and scratches became significantly narrow after 24h; after 48 h, the scratches were completely filled with cells.
Figure 4
Figure 4
TNF-α and VEGF expression analysis in tumor tissue by immunohistochemical assay. TNF-α and VEGF expression were strongly positive (+++) in 40% and 70% ERα+/ERα− ratio groups, compared to 20% and 0% ratio groups (P < 0.05). No staining or number of positively stained cells <10% was considered as negative staining; Light yellow and positively stained cells <11% ≤ 25% were weakly positive (+). Brownish yellow and 26% < positively stained cell ≤50% were medium positive (++); positively stained cells ≤51% was strongly positive (+++).
Figure 5
Figure 5
The ERα+/ERα− ratio plays a critical role in the tumor microenvironment. (a) 1/2: M2 type macrophage polarization at different ER expression levels in tumor microenvironment. M2 macrophage polarization was induced significantly (P < 0.05) in the 70% ERα+/ERα− ratio group. (b) BRCA1 and HER-2 expressing in tumor tissue. BRCA1 and HER-2 expression were induced significantly (P < 0.05) in 40% and 70% ERα+/ERα− ratio groups.
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References

    1. Rahman M. M., Islam M. R., Shohag S., et al. Microbiome in cancer: role in carcinogenesis and impact in therapeutic strategies. Biomedicine and Pharmacotherapy . 2022;149 doi: 10.1016/j.biopha.2022.112898.112898 - DOI - PubMed
    1. Yip C. H., Rhodes A. Estrogen and progesterone receptors in breast cancer. Future Oncology . 2014;10(14):2293–2301. doi: 10.2217/fon.14.110. - DOI - PubMed
    1. Burstein H. J. Systemic therapy for estrogen receptor–positive, HER2-negative breast cancer. New England Journal of Medicine . 2020;383(26):2557–2570. doi: 10.1056/nejmra1307118. - DOI - PubMed
    1. Zhong Y., Ding B., Qian L., Wu W., Wen Y. Hormone receptor expression on endocrine therapy in patients with breast cancer: a meta-analysis. The American Surgeon . 2022;88(1):48–57. doi: 10.1177/0003134820972327. - DOI - PubMed
    1. Takahashi M., Maeda H., Tsujikawa T., et al. 18F-Fluoroestradiol tumor uptake is influenced by structural components in breast cancer. Clinical Nuclear Medicine . 2021;46(11):884–889. doi: 10.1097/rlu.0000000000003835. - DOI - PubMed