Universität zu Köln

Aggarwal, Abhishek, Schulz, Herbert, Manhardt, Teresa, Bilban, Martin, Thakker, Rajesh V. and Kallay, Enikoe (2017). Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium. Biochim. Biophys. Acta-Mol. Cell Res., 1864 (6). S. 987 - 997. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 0006-3002

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Abstract

Colorectal cancer is one of the most common cancers in industrialised societies. Epidemiological studies, animal experiments, and randomized clinical trials have shown that dietary factors can influence all stages of colorectal carcinogenesis, from initiation through promotion to progression. Calcium is one of the factors with a chemoprophylactic effect in colorectal cancer. The aim of this study was to understand the molecular mechanisms of the anti-tumorigenic effects of extracellular calcium ([Ca2+](0)) in colon cancer cells. Gene expression microarray analysis of colon cancer cells treated for 1,4, and 24 h with 2 mM [Ca2+10 identified significant changes in expression of 1571 probe sets (ANOVA, p < 10(-5)). The main biological processes affected by [Ca2+]. were DNA replication, cell division, and regulation of transcription. All factors involved in DNA replication -licensing were significantly downregulated by [Ca2+](0). Furthermore, we show that the calcium-sensing receptor (CaSR), a G protein-coupled receptor is a mediator involved in this process. To test whether these results were physiologically relevant, we fed mice with a standard diet containing low (0.04%), intermediate (0.1%), or high (0.9%) levels of dietary calcium. The main molecules regulating replication licensing were inhibited also in vivo, in the colon of mice fed high calcium diet. We show that among the mechanisms behind the chemopreventive effect of [[Ca2+](0) is inhibition of replication licensing, a process often deregulated in neoplastic transformation. Our data suggest that dietary calcium is effective in preventing replicative stress, one of the main drivers of cancer and this process is mediated by the calcium sensing receptor. (C) 2017 Published by Elsevier B.V.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Aggarwal, Abhishek UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Manhardt, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Bilban, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Thakker, Rajesh V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kallay, Enikoe UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-229411
DOI:	10.1016/j.bbamcr.2017.01.017
Journal or Publication Title:	Biochim. Biophys. Acta-Mol. Cell Res.
Volume:	1864
Number:	6
Page Range:	S. 987 - 997
Date:	2017
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	0006-3002
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTESTINAL EPITHELIAL-CELLS; VITAMIN-D-RECEPTOR; COLON-CANCER; SENSING RECEPTOR; GENE-EXPRESSION; DIETARY CALCIUM; DAIRY-PRODUCTS; UNITED-STATES; CARCINOMA CELLS; IN-VITRO Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22941