ORAI1 and ORAI3 in Breast Cancer Molecular Subtypes and the Identification of ORAI3 as a Hypoxia Sensitive Gene and a Regulator of Hypoxia Responses
Abstract
:1. Introduction
2. Material and Methods
2.1. Cell Culture
2.2. Real-Time RT-PCR
2.3. Immunoblotting
2.4. siRNA-Mediated Silencing
2.5. Measurement of Cytosolic Free Ca2+
2.6. Cell Migration Assay
2.7. Development of MDA-MB-468-GCaMP6m Cell Line
2.8. Assessment of Spontaneous Ca2+ Transients
2.9. ORAI3 Promoter Analysis
2.10. Analysis of ORAI1 and ORAI3 Expression in Breast Tumors
2.11. Patient Survival Analysis
2.12. RNA Sequencing Analysis
2.13. Statistical Analysis
3. Results
3.1. ORAI1 and ORAI3 in Breast Cancer Molecular Subtypes
3.2. Hypoxia Induces ORAI3 Expression
3.3. HIF1α Controls the Hypoxic Expression of ORAI3
3.4. ORAI3 Is Involved in the Hypoxic Regulation of Genes Associated with Cell Migration and Inflammatory/Immune Responses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Azimi, I.; Milevskiy, M.J.G.; Chalmers, S.B.; Yapa, K.T.D.S.; Robitaille, M.; Henry, C.; Baillie, G.J.; Thompson, E.W.; Roberts-Thomson, S.J.; Monteith, G.R. ORAI1 and ORAI3 in Breast Cancer Molecular Subtypes and the Identification of ORAI3 as a Hypoxia Sensitive Gene and a Regulator of Hypoxia Responses. Cancers 2019, 11, 208. https://doi.org/10.3390/cancers11020208
Azimi I, Milevskiy MJG, Chalmers SB, Yapa KTDS, Robitaille M, Henry C, Baillie GJ, Thompson EW, Roberts-Thomson SJ, Monteith GR. ORAI1 and ORAI3 in Breast Cancer Molecular Subtypes and the Identification of ORAI3 as a Hypoxia Sensitive Gene and a Regulator of Hypoxia Responses. Cancers. 2019; 11(2):208. https://doi.org/10.3390/cancers11020208
Chicago/Turabian StyleAzimi, Iman, Michael J.G. Milevskiy, Silke B. Chalmers, Kunsala T.D.S. Yapa, Mélanie Robitaille, Christopher Henry, Gregory J. Baillie, Erik W. Thompson, Sarah J. Roberts-Thomson, and Gregory R. Monteith. 2019. "ORAI1 and ORAI3 in Breast Cancer Molecular Subtypes and the Identification of ORAI3 as a Hypoxia Sensitive Gene and a Regulator of Hypoxia Responses" Cancers 11, no. 2: 208. https://doi.org/10.3390/cancers11020208