1. Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis
- Author
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Jürgen Veeck, Oliver Galm, C Huszka, Eva Klopocki, Matthias Dürst, Edgar Dahl, O Camara, Ruth Knüchel, Frank Wiesmann, H An, Glen Kristiansen, Dieter Niederacher, and Beate Betz
- Subjects
Adult ,Cancer Research ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Epigenesis, Genetic ,chemistry.chemical_compound ,Breast cancer ,Secreted frizzled-related protein 1 ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Gene Silencing ,skin and connective tissue diseases ,Molecular Biology ,Aged ,Glycoproteins ,Aged, 80 and over ,Intracellular Signaling Peptides and Proteins ,Wnt signaling pathway ,Cancer ,DNA Methylation ,Middle Aged ,medicine.disease ,Demethylating agent ,Gene Expression Regulation, Neoplastic ,Wnt Proteins ,chemistry ,DNA methylation ,Cancer research ,Female ,Ovarian cancer ,Carcinogenesis - Abstract
The canonical Wnt signalling pathway plays a key role during embryogenesis and defects in this pathway have been implicated in the pathogenesis of various types of tumours, including breast cancer. The gene for secreted frizzled-related protein 1 (SFRP1) encodes a soluble Wnt antagonist and is located in a chromosomal region (8p22–p12) that is often deleted in breast cancer. In colon, lung, bladder and ovarian cancer SFRP1 expression is frequently inactivated by promoter methylation. We have previously shown that loss of SFRP1 protein expression is a common event in breast tumours that is associated with poor overall survival in patients with early breast cancer. To investigate the cause of SFRP1 loss in breast cancer, we performed mutation, methylation and expression analysis in human primary breast tumours and breast cell lines. No SFRP1 gene mutations were detected. However, promoter methylation of SFRP1 was frequently observed in both primary breast cancer (61%, n=130) and cell lines analysed by methylation-specific polymerase chain reaction (MSP). We found a tight correlation (P
- Published
- 2006