Epigenetic regulation of the expression of the novel stem cell marker CDCP1 in cancer cells

• Published in: The Journal of pathology Vol. 210; no. 1; pp. 75 - 84
• Main Authors: Ikeda, J-i, Morii, E, Kimura, H, Tomita, Y, Takakuwa, T, Hasegawa, J-i, Kim, Y-K, Miyoshi, Y, Noguchi, S, Nishida, T, Aozasa, K
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2006
• Subjects: Adenocarcinoma - genetics; Antigens, CD - analysis; Antigens, CD - genetics; Antigens, Neoplasm - genetics; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Breast Neoplasms - genetics; cancer; CDCP1; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - genetics; Cell Line, Tumor; clinical samples; CpG Islands - genetics; Epigenesis, Genetic - genetics; Female; Gene Expression Regulation, Neoplastic - genetics; Humans; Immunohistochemistry - methods; Ki-67 Antigen - genetics; Leukemia - genetics; Lymphoma - genetics; Methylation; Neoplasm Proteins - analysis; Neoplasm Proteins - genetics; Promoter Regions, Genetic - genetics; Reverse Transcriptase Polymerase Chain Reaction - methods; Transcription, Genetic - genetics; transcriptional regulation
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2026

CDCP1 is a novel stem cell marker that is expressed in several types of cancer. The mechanisms by which CDCP1 expression is regulated, and the clinical implications of this marker, have not been clarified. In this report, we examine the epigenetic regulation of CDCP1 expression in cell lines and clinical samples from patients with breast cancer. Many CpG sequences were localized around the transcription initiation site of CDCP1. These CpG motifs were found to be poorly methylated in cell lines with high levels of CDCP1 expression and heavily methylated in cell lines with low levels of CDCP1 expression. The in vitro methylation of CpG sites decreased CDCP1 promoter activity, and the addition of a demethylating reagent restored activity. In 25 breast cancer samples, an inverse correlation was noted between the CDCP1 expression level and the proportion of methylated to non‐methylated CpG sites. Tumours with high‐level CDCP1 expression showed higher levels of proliferation, as revealed by immunohistochemical detection of the MIB‐1 antigen, than tumours with low‐level CDCP1 expression. These findings indicate that the expression of CDCP1 is regulated by methylation of its promoter region in tumours. CDCP1 expression may prove to be useful in the further characterization of cancers. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.