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ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells

Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, 71500 Heraklion, Greece
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Academic Editor: Alessandro Cannavo
Int. J. Mol. Sci. 2021, 22(14), 7603; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147603
Received: 15 June 2021 / Revised: 6 July 2021 / Accepted: 9 July 2021 / Published: 16 July 2021
Inflammation is important for the initiation and progression of breast cancer. We have previously reported that in monocytes, estrogen regulates TLR4/NFκB-mediated inflammation via the interaction of the Erα isoform ERα36 with GPER1. We therefore investigated whether a similar mechanism is present in breast cancer epithelial cells, and the effect of ERα36 expression on the classic 66 kD ERα isoform (ERα66) functions. We report that estrogen inhibits LPS-induced NFκB activity and the expression of downstream molecules TNFα and IL-6. In the absence of ERα66, ERα36 and GPER1 are both indispensable for this effect. In the presence of ERα66, ERα36 or GPER1 knock-down partially inhibits NFκB-mediated inflammation. In both cases, ERα36 overexpression enhances the inhibitory effect of estrogen on inflammation. We also verify that ERα36 and GPER1 physically interact, especially after LPS treatment, and that GPER1 interacts directly with NFκB. When both ERα66 and ERα36 are expressed, the latter acts as an inhibitor of ERα66 via its binding to estrogen response elements. We also report that the activation of ERα36 leads to the inhibition of breast cancer cell proliferation. Our data support that ERα36 is an inhibitory estrogen receptor that, in collaboration with GPER1, inhibits NFκB-mediated inflammation and ERα66 actions in breast cancer cells. View Full-Text
Keywords: breast cancer; estrogen receptor alpha 36; GPER1; TLR4; NF-κB; TNFα; IL-6 breast cancer; estrogen receptor alpha 36; GPER1; TLR4; NF-κB; TNFα; IL-6
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MDPI and ACS Style

Notas, G.; Panagiotopoulos, A.; Vamvoukaki, R.; Kalyvianaki, K.; Kiagiadaki, F.; Deli, A.; Kampa, M.; Castanas, E. ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells. Int. J. Mol. Sci. 2021, 22, 7603. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147603

AMA Style

Notas G, Panagiotopoulos A, Vamvoukaki R, Kalyvianaki K, Kiagiadaki F, Deli A, Kampa M, Castanas E. ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells. International Journal of Molecular Sciences. 2021; 22(14):7603. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147603

Chicago/Turabian Style

Notas, George, Athanasios Panagiotopoulos, Rodanthi Vamvoukaki, Konstantina Kalyvianaki, Foteini Kiagiadaki, Alexandra Deli, Marilena Kampa, and Elias Castanas. 2021. "ERα36–GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells" International Journal of Molecular Sciences 22, no. 14: 7603. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147603

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