Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and Induces Estrogen Receptor Alpha Isoform Variation
Abstract
:1. Introduction
2. Results
2.1. Enhanced Expression of AGO2 Is Associated with an ERα− and Luminal B Breast Cancer Phenotype
2.2. Overexpression of AGO2 Represses Estrogen Signaling through Inhibition of ERα in Vitro but Does Not Diminish E2-Stimulated Tumorigenesis in Vivo
2.3. AGO2 Expression Selectively Increases ERα-36 Isoform Expression
3. Discussion
4. Materials and Methods
4.1. Cells and Reagents
4.2. Transfection of MCF-7 Cell Line
4.3. RNA Extraction and Quantitative Real Time RT-PCR
4.4. Western Blot
4.5. Animal Studies
4.6. Immunohistochemistry (IHC)
4.7. MicroRNA PCR Array
4.8. Data Sources
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AF | activation function |
AGO2 | argonaute 2 |
EGFR | epidermal growth factor receptor |
ERα | estrogen receptor |
HER2/neu | V-Erb-B2 Erythroblastic Leukemia Viral Oncogene Homolog 2 |
MAPK | mitogen activated protein kinase |
mTOR | mammalian target of rapamycin |
miRNAs | microRNAs |
PGR | progesterone receptor |
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# | Population and Event Criteria 1 | p Value | HR | 95% CI | Good Prognosis RNA Level | No. Patients | ||
---|---|---|---|---|---|---|---|---|
1 | N- | ERm | AE | <0.0001 | 1.25 | 1.15–1.36 | Low | 1799 |
2 | Nm | ERm | MR | <0.0001 | 1.21 | 1.12–1.30 | Low | 2565 |
3 | Nm | ERm | AE | <0.0001 | 1.16 | 1.10–1.24 | Low | 3300 |
4 | N− | ER+ | AE | <0.0001 | 1.30 | 1.17–1.45 | Low | 1388 |
5 | Nm | ER+ | MR | <0.0001 | 1.26 | 1.14–1.39 | Low | 1929 |
6 | N− | ER+ | MR | <0.0001 | 1.33 | 1.17–1.52 | Low | 1146 |
7 | N− | ERm | MR | <0.0001 | 1.24 | 1.12–1.37 | Low | 1492 |
8 | Nm | ER+ | AE | <0.0001 | 1.18 | 1.09–1.28 | Low | 2483 |
9 | N+ | ERm | MR | 0.0549 | 1.13 | 1.00–1.29 | Low | 842 |
10 | N+ | ER+ | MR | 0.1156 | 1.14 | 0.97–1.34 | -- | 652 |
11 | N− | ER | AE | 0.1564 | 1.13 | 0.95–1.33 | -- | 390 |
12 | Nm | ER | AE | 0.4186 | 1.05 | 0.94–1.17 | -- | 774 |
13 | N+ | ER | AE | 0.4618 | 0.93 | 0.77–1.13 | -- | 226 |
14 | N+ | ER | MR | 0.5316 | 0.92 | 0.72–1.19 | -- | 173 |
15 | Nm | ER | MR | 0.6938 | 1.03 | 0.89–1.18 | -- | 601 |
16 | N+ | ER+ | AE | 0.7713 | 0.98 | 0.86–1.11 | -- | 815 |
17 | N− | ER | MR | 0.8048 | 1.02 | 0.84–1.24 | -- | 330 |
18 | N+ | ERm | AE | 0.8467 | 1.01 | 0.91–1.12 | -- | 1058 |
11 | N− | ER | AE | 0.1564 | 1.13 | 0.95–1.33 | -- | 390 |
12 | Nm | ER | AE | 0.4186 | 1.05 | 0.94–1.17 | -- | 774 |
13 | N+ | ER | AE | 0.4618 | 0.93 | 0.77–1.13 | -- | 226 |
14 | N+ | ER | MR | 0.5316 | 0.92 | 0.72–1.19 | -- | 173 |
15 | Nm | ER | MR | 0.6938 | 1.03 | 0.89–1.18 | -- | 601 |
16 | N+ | ER+ | AE | 0.7713 | 0.98 | 0.86–1.11 | -- | 815 |
17 | N− | ER | MR | 0.8048 | 1.02 | 0.84–1.24 | -- | 330 |
18 | N+ | ERm | AE | 0.8467 | 1.01 | 0.91–1.12 | -- | 1058 |
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Conger, A.K.; Martin, E.C.; Yan, T.J.; Rhodes, L.V.; Hoang, V.T.; La, J.; Anbalagan, M.; Burks, H.E.; Rowan, B.G.; Nephew, K.P.; et al. Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and Induces Estrogen Receptor Alpha Isoform Variation. Non-Coding RNA 2016, 2, 8. https://doi.org/10.3390/ncrna2030008
Conger AK, Martin EC, Yan TJ, Rhodes LV, Hoang VT, La J, Anbalagan M, Burks HE, Rowan BG, Nephew KP, et al. Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and Induces Estrogen Receptor Alpha Isoform Variation. Non-Coding RNA. 2016; 2(3):8. https://doi.org/10.3390/ncrna2030008
Chicago/Turabian StyleConger, Adrienne K., Elizabeth C. Martin, Thomas J. Yan, Lyndsay V. Rhodes, Van T. Hoang, Jacqueline La, Muralidharan Anbalagan, Hope E. Burks, Brian G. Rowan, Kenneth P. Nephew, and et al. 2016. "Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and Induces Estrogen Receptor Alpha Isoform Variation" Non-Coding RNA 2, no. 3: 8. https://doi.org/10.3390/ncrna2030008