Ectopic expression of P-Cadherin correlates with promoter hypomethylation early in colorectal carcinogenesis and enhanced intestinal crypt fission in mice

P-cadherin is normally expressed in the basal layer of squamous epithelia and absent from the healthy intestine and colon. We have previously shown it to be expressed in all inflamed, hyperplastic and dysplastic intestinal and colonic mucosa. This study aimed to better understand the mechanisms cont...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2008-10, Vol.68 (19), p.7760-7768
Main Authors: Milicic, Anita, Harrison, Lea-Anne, Goodlad, Robert A., Hardy, Robert G., Nicholson, Anna M., Presz, Michal, Sieber, Oliver, Santander, Sonia, Pringle, James H., Mandir, Nikki, East, Philip, Obszynska, Jolanta, Sanders, Scott, Piazuelo, Elena, Shaw, Jacqui, Harrison, Rebecca, Tomlinson, Ian P., McDonald, Stuart A. C., Wright, Nicholas A., Jankowski, Janusz A. Z.
Format: Article
Language:English
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Summary:P-cadherin is normally expressed in the basal layer of squamous epithelia and absent from the healthy intestine and colon. We have previously shown it to be expressed in all inflamed, hyperplastic and dysplastic intestinal and colonic mucosa. This study aimed to better understand the mechanisms controlling the expression of P-cadherin and the biological effects of its ectopic presence in the intestine and colon. We investigated the CpG methylation status of the P-cadherin (CDH3) promoter and P-cadherin mRNA and protein expression in cases of familial and sporadic colorectal cancer. The CDH3 promoter was hypomethylated in colonic aberrant crypt foci, colorectal cancer and occasionally in the normal epithelium adjacent to cancer, demonstrating a potential “field effect” of cancerisation. The hypomethylation was associated with induction of P-cadherin expression in the neoplastic colon (p
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-0020