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Originally published In Press as doi:10.1074/jbc.M201747200 on May 1, 2002
J. Biol. Chem., Vol. 277, Issue 29, 26310-26320, July 19, 2002
Expression of Endomembrane Calcium Pumps in Colon and
Gastric Cancer Cells
INDUCTION OF SERCA3 EXPRESSION DURING DIFFERENTIATION*
Pascal
Gélébart §,
Tünde
Kovács¶ ,
Jean-Philippe
Brouland**,
Roosje
van
Gorp ,
Johannes
Grossmann ,
Nathalie
Rivard§§,
Yves
Panis¶¶,
Virginie
Martin ,
Raymonde
Bredoux ,
Jocelyne
Enouf , and
Béla
Papp 
From the Unité 348 INSERM, IFR-6,
Hôpital Lariboisière, 75010 Paris, France, ¶ National
Institute of Haematology and Immunology, Daròczi ùt 24, 1113 Budapest, Hungary, ** Service d'Anatomie Pathologique,
Hôpital Lariboisière, 75010 Paris, France,
 Klinik und Poliklinik für Innere
Medizin I, Klinikum der Universität Regensburg, 93042 Regensburg, Germany, §§ Faculté de
Médecine, Université de Sherbrooke, 3001, 12e
Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada, and
¶¶ Service de Chirurgie Générale et Digestive,
Hôpital Lariboisière, 75010 Paris, France
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.
*
This work was supported in part by INSERM, by the
Association pour la Recherche sur le Cancer, France, by Nestlé,
France, by Research Grant T 032766 from OTKA, Hungary, and by APRIFEL, France.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
We dedicate our work to the memory of all victims of the tragedy of
September 11, 2001.
§
Recipient of a doctoral fellowship from Nestlé, France, and
from APRIFEL.
Recipient of the Bolyai János Research Fellowship of the
Hungarian Academy of Sciences.

To whom correspondence should be addressed: U. 348 INSERM, Hôpital Lariboisière, 8 Rue Guy Patin, 75010 Paris,
France. Fax: 33-1- 49-95-85-79; E-mail:
bela.papp@inserm.lrb.ap-hop-paris.fr.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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