title: A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.
abstract: The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.
authors.affiliation: a Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga # 15, Col. Sección XVI, México, D.F. 14000, México.
authors.forename: V
authors.initials: V
authors.lastname: Cázares-Ordoñez
authors.forename: R J
authors.initials: RJ
authors.lastname: González-Duarte
authors.forename: L
authors.initials: L
authors.lastname: Díaz
authors.forename: M
authors.initials: M
authors.lastname: Ishizawa
authors.forename: S
authors.initials: S
authors.lastname: Uno
authors.forename: V
authors.initials: V
authors.lastname: Ortíz
authors.forename: M L
authors.initials: ML
authors.lastname: Ordoñez-Sánchez
authors.forename: M
authors.initials: M
authors.lastname: Makishima
authors.forename: F
authors.initials: F
authors.lastname: Larrea
authors.forename: E
authors.initials: E
authors.lastname: Avila
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D006801:Humans; D018167:Receptors, Calcitriol / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D030181:Vitamin D Response Element / Q000235:genetics*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D018167:Receptors, Calcitriol; D014157:Transcription Factors; D002117:Calcitriol
keywords: 1,25-dihydroxyvitamin D3; 1,25-dihydroxyvitamine D3; VDIR; WSTF; canal K+ hEAG1; cancer cervical; cervical cancer; hEAG K+ channel