ArticleMolecular endocrinology (Baltimore, Md.)2011
The two-pore domain potassium channel KCNK5: induction by estrogen receptor alpha and role in proliferation of breast cancer cells.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.Cell reports. Medicine · 2024Pooled it
- Mechanisms of intracellular pH gating and local anesthetic inhibition of the two-pore domain KProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-nucleus analysis of menstrual fluid highlights gene expression differences in epithelial cells of endometriosis donors.BMC medicine · 2026Article
- A SWI/SNF complex-related genes signature predicts prognosis and immune infiltration in ccRCC with KCNK5 as a novel biomarker.Scientific reports · 2025Article
- LDLRAD4 is a potential diagnostic and prognostic biomarker correlated with immune infiltration in myelodysplastic syndromes.Frontiers in genetics · 2025Article
- Identification of mitochondrial permeability transition-related lncRNAs as quantitative biomarkers for the prognosis and therapy of breast cancer.Frontiers in genetics · 2025Article
- The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b.PLoS biology · 2024Article
- Potassium channels as novel molecular targets in hepatocellular carcinoma (Review).Oncology reports · 2023Review
- High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer.Breast cancer research and treatment · 2023Article
- KCNK9 mediates the inhibitory effects of genistein on hepatic metastasis from colon cancer.Clinics (Sao Paulo, Brazil) · 2023Article
- Overexpression of Estrogen Receptor α in Mammary Glands of Aging Mice Is Associated with a Proliferative Risk Signature and Generation of Estrogen Receptor α-Positive Mammary Adenocarcinomas.The American journal of pathology · 2023Article
- Potassium Channels as a Target for Cancer Therapy: Current Perspectives.OncoTargets and therapy · 2022Review
- Integrative Analysis of KCNK Genes and Establishment of a Specific Prognostic Signature for Breast Cancer.Frontiers in cell and developmental biology · 2022Article
- Effect ofFrontiers in genetics · 2022Article
- A "Target Class" Screen to Identify Activators of Two-Pore Domain Potassium (K2P) Channels.SLAS discovery : advancing life sciences R & D · 2021Article
- Article
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
- Pathological role of ion channels and transporters in the development and progression of triple-negative breast cancer.Cancer cell international · 2020Review
- The correlation and role analysis of KCNK2/4/5/15 in Human Papillary Thyroid Carcinoma microenvironment.Journal of Cancer · 2020Article
- Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The growth of many human breast tumors requires the proliferative effect of estrogen acting via the estrogen receptor α (ERα). ERα signaling is therefore a clinically important target for breast cancer prevention and therapeutics. Although extensively studied, the mechanism by which ERα promotes proliferation remains to be fully established. We observed an up-regulation of transcript encoding the pH-sensitive two-pore domain potassium channel KCNK5 in a screen for genes stimulated by 17β-estradiol (E2) in the ERα(+) breast cancer cell lines MCF-7 and T47D. KCNK5 mRNA increased starting 1 h after the onset of E2 treatment, and protein levels followed after 12 h. Estrogen-responsive elements are found in the enhancer region of KCNK5, and chromatin immunoprecipitation assays revealed binding of ERα to the KCNK5 enhancer in E2-treated MCF-7 cells. Cells treated with E2 also showed increases in the amplitude of pH-sensitive potassium currents, as assessed by whole-cell recordings. These currents are blocked by clofilium. Although confocal microscopy suggested that most of the channels are located in intracellular compartments, the increase in macroscopic currents suggests that E2 treatment increases the number of active channels at the cell surface. Application of small interfering RNA specific for KCNK5 decreased pH-sensitive potassium currents and also reduced the estrogen-induced proliferation of T47D cells. We conclude that E2 induces the expression of KCNK5 via ERα(+) in breast cancer cells, and this channel plays a role in regulating proliferation in these cell lines. KCNK5 may therefore represent a useful target for treatment, for example, of tamoxifen-resistant breast cancer.
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