Receptors

13 pages, 1832 KiB

Open AccessBrief Report

Expression of the Purinergic P2X7 Receptor in Murine MOPC315.BM Myeloma Cells

by Eva Risborg Høyer, Melisa Demir, Lasse Kristoffer Bak, Niklas Rye Jørgensen and Ankita Agrawal

Receptors 2023, 2(3), 191-203; https://doi.org/10.3390/receptors2030013 - 7 Sep 2023

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The adenosine-5’ triphosphate (ATP)-gated, ion channel, P2X receptor superfamily has seven members expressed by many cancer types. Subtype 7 (P2X7 receptor) is expressed consistently at levels higher than in comparatively healthy tissues. Moreover, transcript variant heterogeneity is associated with drug resistance. We have previously described the role of the P2X7 receptor in myeloma, a rare blood disease that uniquely presents with aggressive bone destruction. In this study, we used known agonists of the P2X7 receptor to induce calcium influx and YO-PRO-1 uptake in murine MOPC315.BM myeloma cells as readouts of P2X7 receptor-mediated channel activation and pore formation, respectively. Neither ATP- nor BzATP-induced calcium influx and YO-PRO-1 indicated an absence of the P2X7 receptor function on MOPC315.BM cells. TaqMan revealed low (Ct > 35) P2rx7 but high P2rx4 gene expression in MOPC315.BM; the latter was downregulated with BzATP treatment. The concomitant downregulation of CD39/Entpd1, Icam-1, and Nf-kb1 and the upregulation of Casp-1 genes regulated during purinergic signaling and with established roles in myeloma progression suggest P2RX4-mediated survival adaptation by cancer cells. Further studies are needed to characterize the P2RX4 pharmacology on MOPC315.BM since transcriptional regulation may be utilized by cancer cells to overcome the otherwise toxic effects of high extracellular ATP. Full article

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15 pages, 4021 KiB

Open AccessFeature PaperArticle

Estrogen Receptor β Isoforms Regulate Chemotherapy Resistance and the Cancer Stem Cell Population in Prostate Cancer Cells

by Jessica H. Stevens, Ayesha Bano, Lamia Bensaoula, Anders M. Strom and Jan-Åke Gustafsson

Receptors 2023, 2(3), 176-190; https://doi.org/10.3390/receptors2030012 - 1 Aug 2023

Cited by 1 | Viewed by 1515

Abstract

Estrogen receptor beta 1 (ERβ1) is a ligand-activated nuclear receptor, which has been shown to maintain tissue differentiation in the normal prostate, and regulate androgen response and increase expression of tumor suppressors in prostate cancer cell lines. There are three shorter isoforms of ERβ expressed in the human prostate, ERβ2, ERβ4, and ERβ5, which have already been implicated in chemotherapy resistance and disease progression, suggesting a possible oncogenic role. Their ligand-binding domain (LBD) is truncated, so they are unable to activate canonical ERβ1 signaling pathways; however, they were shown to participate in hypoxic signaling and to induce a gene expression signature associated with stemness and hypoxia. To elucidate the role of the truncated ERβ isoforms in prostate cancer, we created a knockout of all isoforms, as well as a truncation of the LBD, to remove the function of ERβ1. We showed that the removal of all isoforms leads to a decrease in the expression of cancer stem cell (CSC)-associated genes, decreased chemotherapy resistance, and a decrease in the CSC population, based on sphere formation ability and SORE6 (CSC reporter) activity, while removing the LBD function only had the opposite effect. Our results suggest a more aggressive phenotype in prostate cancer cell lines expressing ERβ variants. Full article

(This article belongs to the Special Issue Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson)

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10 pages, 1323 KiB

Open AccessOpinion

From Antibodies to Crystals: Understanding the Structure of the Glucocorticoid Receptor and Related Proteins

by Iain J. McEwan

Receptors 2023, 2(3), 166-175; https://doi.org/10.3390/receptors2030011 - 3 Jul 2023

Cited by 2 | Viewed by 1465

Abstract

The steroid/thyroid hormone or nuclear receptor superfamily is quickly approaching its 40th anniversary. During this period, we have seen tremendous progress being made in our understanding of the mechanisms of action of these physiologically important proteins in the field of health and disease. Critical to this has been the insight provided by ever more detailed structural examination of nuclear receptor proteins and the complexes they are responsible for assembling on DNA. In this article, I will focus on the contributions made by Jan-Åke Gustafsson and colleagues at the Karolinska Institute (Sweden) and, more recently, the University of Houston (USA), to this area of nuclear receptor research. Full article

(This article belongs to the Special Issue Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson)

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Receptors, Volume 2, Issue 3 (September 2023) – 3 articles

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