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

Details

Serval ID
serval:BIB_18A9CCB597A6
Type
Article: article from journal or magazin.
Collection
Publications
Title
The loss of sarco/endoplasmic reticulum calcium transport ATPase 3 expression is an early event during the multistep process of colon carcinogenesis.
Journal
American Journal of Pathology
Author(s)
Brouland J.P., Gélébart P., Kovàcs T., Enouf J., Grossmann J., Papp B.
ISSN
0002-9440 (Print)
ISSN-L
0002-9440
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
167
Number
1
Pages
233-242
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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/beta-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/beta-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.
Keywords
Adenomatous Polyposis Coli Protein/genetics, Blotting, Western, Calcium/metabolism, Calcium-Transporting ATPases/biosynthesis, Cell Line, Tumor, Cell Transformation, Neoplastic, Colonic Neoplasms/enzymology, Colonic Polyps/enzymology, Cytoskeletal Proteins/genetics, DNA-Binding Proteins, Endoplasmic Reticulum/metabolism, Humans, Immunohistochemistry, Intestinal Mucosa/enzymology, Intestinal Mucosa/metabolism, Sarcoplasmic Reticulum Calcium-Transporting ATPases, TCF Transcription Factors, Trans-Activators/genetics, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transfection, Transgenes, Tumor Markers, Biological/analysis, beta Catenin
Pubmed
Web of science
Create date
13/10/2015 9:51
Last modification date
20/08/2019 12:49
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