title: Regulation of the calcium-sensing receptor expression by 1,25-dihydroxyvitamin D3, interleukin-6, and tumor necrosis factor alpha in colon cancer cells.
abstract: Anti-proliferative effects of calcium in the colon are mediated, at least in part, via the calcium-sensing receptor (CaSR), a vitamin D target gene. The expression of CaSR decreases during colorectal tumor progression and the mechanisms regulating its expression are poorly understood. The CaSR promoter harbors vitamin D elements responsive to 1,25-dihydroxyvitamin D3 (1,25D3) and NF-κB, STAT, and SP1 binding sites accounting for responsiveness to proinflammatory cytokines. Therefore, in the current study we investigated the impact of 1,25D3, tumor necrosis factor alpha (TNFα), and interleukin (IL)-6 on CaSR expression in a differentiated (Caco2/AQ) and in a moderately differentiated (Coga1A) colon cancer cell line. 1,25D3 induced CaSR expression in both cell lines. Treatment with TNFα was accompanied by a 134-fold induction of CaSR in Coga1A (p<0.01). In Caco2/AQ cells the expression of CaSR was upregulated also by IL-6 (3.5-fold). Our data demonstrated transcriptional and translational activation of the CaSR by 1,25D3, TNFα, and IL-6 in a time- and cell line-dependent manner. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: irfete.fetahu@meduniwien.ac.at.
authors.forename: Irfete S
authors.initials: IS
authors.lastname: Fetahu
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: doris.hummel@meduniwien.ac.at.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Hummel
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: teresa.manhardt@meduniwien.ac.at.
authors.forename: Teresa
authors.initials: T
authors.lastname: Manhardt
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: abhishek.aggarwal@meduniwien.ac.at.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: sabina.baumgartner-parzer@meduniwien.ac.at.
authors.forename: Sabina
authors.initials: S
authors.lastname: Baumgartner-Parzer
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. Electronic address: enikoe.kallay@meduniwien.ac.at.
authors.forename: Enikő
authors.initials: E
authors.lastname: Kállay
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; D015850:Interleukin-6; D044169:Receptors, Calcium-Sensing; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol
keywords: 1,25-dihydroxyvitamin D(3); Calcium-sensing receptor; Colon cancer; Inflammation; Interleukin-6; Tumor necrosis factor alpha