title: Selective upregulation of the expression of plasma membrane calcium ATPase isoforms upon differentiation and 1,25(OH)2D3-vitamin treatment of colon cancer cells.
abstract: We have previously presented co-expression of the plasma membrane calcium ATPase isoforms 4b (PMCA4b) and 1b (PMCA1b) in colon carcinoma cells, and selective upregulation of PMCA4b during differentiation initiated by short chain fatty acids or post-confluent growth. Here we show that the induction of PMCA4b expression is a characteristic feature of the post-confluency-induced differentiation of both enterocyte-type and goblet cell-type colon cancer cells. Vitamin D3 (1,25(OH)2D3) is a well-known regulator of intestinal Ca(2+) absorption and of basic cell functions such as growth and differentiation in various cell types. As PMCA proteins are involved both in intestinal Ca(2+) absorption and adenocarcinoma cell differentiation, we investigated the effect of 1,25(OH)2D3 on PMCA expression in enterocyte-like colon carcinoma cells, and monitored its effect on the expression of various differentiation markers. 1,25(OH)2D3 stimulated PMCA1b, but not PMCA4b expression without modulating the expression of the majority of the differentiation markers examined. Caco-2 cells differentiated in post-confluent cultures present normal enterocyte-like intestinal epithelial phenotype. To better understand the role of PMCA proteins in vectorial Ca(2+) transport by enterocytes, we also studied their subcellular localization in mature polarized Caco-2 cells. Both PMCA isoforms were located to the basolateral membrane, and the PMCA-specific immunofluorescent signal was significantly higher in vitamin D3-treated cells, underlining the 1,25(OH)2D3-induced upregulation of PMCA (presumably 1b isoform) expression in differentiated Caco-2 cells. We suggest that while PMCA1b has a housekeeping function in colon cancer cells, PMCA4b participates in the reorganization of the Ca(2+) signalling machinery during cell differentiation. The subcellular localization of PMCA1b and its selective 1,25(OH)2D3-dependent upregulation indicate that this isoform may have a specific role in 1,25(OH)2D3-stimulated intestinal Ca(2+) absorption.
authors.affiliation: Membrane Biology Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Polett
authors.initials: P
authors.lastname: Ribiczey
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR U978, Bobigny, France; Université Paris-13, PRES Sorbonne Paris-Cité, Bobigny, France.
authors.forename: Béla
authors.initials: B
authors.lastname: Papp
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Homolya
authors.affiliation: Molecular Oncology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; Second Institute of Pathology, Semmelweis University, Budapest, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Enyedi
authors.affiliation: Membrane Biology Research Group, Hungarian Academy of Sciences, Budapest, Hungary; Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary. Electronic address: kovacs.tunde@med.semmelweis-univ.hu.
authors.forename: Tünde
authors.initials: T
authors.lastname: Kovács
mesh_terms: D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D016764:Cell Polarity; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D010641:Phenotype; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: C506952:ATP2B1 protein, human; C507517:ATP2B4 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; D002117:Calcitriol; D002118:Calcium
keywords: 1,25(OH)(2)D(3)-vitamin; Calcium ATPase; Colon cancer cells; Differentiation; Expression; PMCA isoforms