Please use this identifier to cite or link to this item: doi:10.22028/D291-29521
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Title: Epigenetic regulation of Amphiregulin and Epiregulin in colorectal cancer
Author(s): Bormann, Felix
Stinzing, Sebastian
Tierling, Sascha
Morkel, Markus
Markelova, Maria Rivera
Walter, Jörn Erik
Weichert, Wilko
Roßner, Florian
Kuhn, Natalia
Perner, Juliane
Dietz, Johanna
Ispasanie, Sylvia
Dietel, Manfred
Schäfer, Reinhold
Heinemann, Volker
Sers, Christine
Language: English
Title: International journal of cancer
Volume: 144
Issue: 3
Startpage: 569
Endpage: 581
Publisher/Platform: Wiley-Blackwell - STM
Year of Publication: 2018
Publikation type: Journal Article
Abstract: Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs. Upon treatment of colorectal cancer cells with 5-aza-2'-desoxycytidine, methylation decreases at specific intragenic CpGs accompanied by upregulation of AREG and EREG gene expression. The same AREG gene-body methylation was also found in human colorectal cancer samples and is independent of KRAS and NRAS mutations. Methylation is specifically decreased in the tumor epithelial compartment as compared to stromal tissue and normal epithelium. Investigation of a promoter/enhancer function of the AREG exon 2 region revealed a potential promoter function in reverse orientation. Retrospective comparison of the predictive power of AREG gene-body methylation versus AREG gene expression using samples from colorectal cancer patients treated with anti-EGFR inhibitors with complete clinical follow-up revealed that AREG expression is superior to AREG gene methylation. AREG and EREG genes undergo a complex regulation involving both intragenic methylation and promoter-dependent control.
DOI of the first publication: 10.1002/ijc.31892
Link to this record: hdl:20.500.11880/27909
ISSN: 0020-7136
Date of registration: 26-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Jörn Walter
Collections:Die Universitätsbibliographie

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