Abbreviations: BE, Barrett's esophagus; EAC, esophageal adenocarcinoma; HGD, high-grade dysplasia; MSP, methylation-specific PCR; PKP1, plakophilin-1.
Aberrantly methylated PKP1 in the progression of Barrett's esophagus to esophageal adenocarcinoma†
Article first published online: 14 DEC 2011
Copyright © 2011 Wiley Periodicals, Inc.
Genes, Chromosomes and Cancer
Volume 51, Issue 4, pages 384–393, April 2012
How to Cite
Kaz, A. M., Luo, Y., Dzieciatkowski, S., Chak, A., Willis, J. E., Upton, M. P., Leidner, R. S. and Grady, W. M. (2012), Aberrantly methylated PKP1 in the progression of Barrett's esophagus to esophageal adenocarcinoma. Genes Chromosom. Cancer, 51: 384–393. doi: 10.1002/gcc.21923
- Issue published online: 9 FEB 2012
- Article first published online: 14 DEC 2011
- Manuscript Accepted: 16 NOV 2011
- Manuscript Revised: 4 OCT 2011
- Manuscript Received: 8 JUL 2011
The aberrant DNA methylation of tumor suppressor genes occurs frequently in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) and likely affects the initiation and progression of BE to EAC. In the present study, we discovered PKP1 as a novel methylated gene in EAC and then investigated the role of loss of PKP1, a constituent of the desmosome complex found in stratified epithelial layers, on the behavior of Barrett's esophagus and esophageal adenocarcinoma cells. By using primary esophageal tissue samples we determined that PKP1 was rarely methylated in normal squamous esophagus (5/55; 9.1%) and BE (5/39; 12.8%) and more frequently methylated in Barrett's esophagus with high-grade dysplasia (HGD) or EAC (20/60; 33.3%; P < 0.05). Furthermore, PKP1 levels were decreased in BE and HGD/EAC cases compared to normal squamous esophagus cases. Knockdown of PKP1 in the BE cell lines CP-A and CP-D (both normally express PKP1) resulted in increased cell motility. Thus, PKP1 loss secondary to promoter methylation, as well as other mechanisms, may promote the progression of BE to EAC in a subset of patients via decreased desmosome assembly and increased cell motility. © 2011 Wiley Periodicals, Inc.