title: Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during differentiation.
abstract: Calcium mobilization from the endoplasmic reticulum (ER) into the cytosol is a key component of several signaling networks controlling tumor cell growth, differentiation, or apoptosis. Sarco/endoplasmic reticulum calcium transport ATPases (SERCA-type calcium pumps), enzymes that accumulate calcium in the ER, play an important role in these phenomena. We report that SERCA3 expression is significantly reduced or lost in colon carcinomas when compared with normal colonic epithelial cells, which express this enzyme at a high level. To study the involvement of SERCA enzymes in differentiation, in this work differentiation of colon and gastric cancer cell lines was initiated, and the change in the expression of SERCA isoenzymes as well as intracellular calcium levels were investigated. Treatment of the tumor cells with butyrate or other established differentiation inducing agents resulted in a marked and specific induction of the expression of SERCA3, whereas the expression of the ubiquitous SERCA2 enzymes did not change significantly or was reduced. A similar marked increase in SERCA3 expression was found during spontaneous differentiation of post-confluent Caco-2 cells, and this closely correlated with the induction of other known markers of differentiation. Analysis of the expression of the SERCA3 alternative splice isoforms revealed induction of all three known iso-SERCA3 variants (3a, 3b, and 3c). Butyrate treatment of the KATO-III gastric cancer cells led to higher resting cytosolic calcium concentrations and, in accordance with the lower calcium affinity of SERCA3, to diminished ER calcium content. These data taken together indicate a defect in SERCA3 expression in colon cancers as compared with normal colonic epithelium, show that the calcium homeostasis of the endoplasmic reticulum may be remodeled during cellular differentiation, and indicate that SERCA3 constitutes an interesting new differentiation marker that may prove useful for the analysis of the phenotype of gastrointestinal adenocarcinomas.
authors: Unité 348 INSERM, IFR-6, Hôpital Lariboisière, 75010 Paris, France.
authors: Pascal
authors: P
authors: Gélébart
authors: Tunde
authors: T
authors: Kovács
authors: Jean-Philippe
authors: JP
authors: Brouland
authors: Roosje
authors: R
authors: van Gorp
authors: Johannes
authors: J
authors: Grossmann
authors: Nathalie
authors: N
authors: Rivard
authors: Yves
authors: Y
authors: Panis
authors: Virginie
authors: V
authors: Martin
authors: Raymonde
authors: R
authors: Bredoux
authors: Jocelyne
authors: J
authors: Enouf
authors: Béla
authors: B
authors: Papp
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology; D017398:Alternative Splicing; D000818:Animals; D014408:Biomarkers, Tumor; D002087:Butyrates / Q000494:pharmacology; D018938:Caco-2 Cells; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D003110:Colonic Neoplasms / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011817:Rabbits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013274:Stomach Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D002087:Butyrates; D007527:Isoenzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; C506949:ATP2A3 protein, human; D000252:Calcium-Transporting ATPases