The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis

Jean Philippe Brouland, Pascal Gélébart, T. Kovács, Jocelyne Enouf, Johannes Grossmann, Béla Papp

Research output: Contribution to journalArticle

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Abstract

Calcium accumulation in the endoplasmic reticulum is accomplished by sarco/endoplasmic reticulum calcium transport ATPases (SERCA enzymes). To better characterize the role of SERCA3 in colon carcinogenesis, its expression has been investigated in colonic epithelium, benign lesions, adenomas, and adenocarcinomas. In addition, the regulation of SERCA3 expression was analyzed in the context of the adenomatous polyposis coli/β-catenin/T-cell factor 4 (TCF4) pathway and of specificity protein 1 (Sp1)-like factor-dependent transcription. We report that SERCA3 expression increased along the crypts as cells differentiated in normal colonic mucosa and in hyperplastic polyps, was moderately and heterogeneously expressed in colonic adenomas with expression levels inversely correlated with the degree of dysplasia, was barely detectable in well and moderately differentiated adenocarcinomas, and was absent in poorly differentiated tumors. Inhibition of Sp1-like factor-dependent transcription blocked SERCA3 expression during cell differentiation, and SERCA3 expression was induced by the expression of dominant-negative TCF4 in colon cancer cells. These data link SERCA3 expression to the state of differentiation of colonic epithelial cells, and relate SERCA3 expression, already decreased in adenomas, to enhanced adenomatous polyposis coli/β-catenin/TCF4-dependent signaling and deficient Sp1-like factor-dependent transcription. In conclusion, intracellular calcium homeostasis becomes progressively anomalous during colon carcinogenesis as reflected by deficient SERCA3 expression.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalAmerican Journal of Pathology
Volume167
Issue number1
Publication statusPublished - Jul 2005

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Transcription Factor 7-Like 2 Protein
Calcium-Transporting ATPases
Endoplasmic Reticulum
Adenoma
Catenins
Colon
Carcinogenesis
Adenomatous Polyposis Coli
Transcription Factors
Adenocarcinoma
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Calcium
Proteins
Polyps
Colonic Neoplasms
Cell Differentiation
Mucous Membrane
Homeostasis
Epithelium
Epithelial Cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis. / Brouland, Jean Philippe; Gélébart, Pascal; Kovács, T.; Enouf, Jocelyne; Grossmann, Johannes; Papp, Béla.

In: American Journal of Pathology, Vol. 167, No. 1, 07.2005, p. 233-242.

Research output: Contribution to journalArticle

Brouland, Jean Philippe ; Gélébart, Pascal ; Kovács, T. ; Enouf, Jocelyne ; Grossmann, Johannes ; Papp, Béla. / The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis. In: American Journal of Pathology. 2005 ; Vol. 167, No. 1. pp. 233-242.
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