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[Cancer Research 55, 5195-5199, November 15, 1995]
© 1995 American Association for Cancer Research

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E-Cadherin Expression Is Silenced by DNA Hypermethylation in Human Breast and Prostate Carcinomas1

Jeremy R. Graff, James G. Herman, Rena G. Lapidus, Hemi Chopra, Rosa Xu, David F. Jarrard, William B. Isaacs, Paula M. Pitha, Nancy E. Davidson and Stephen B. Baylin2

The Johns Hopkins Oncology Center [J. R. G., J. G. H., R. G. L. H. C., R. X., P. M. P., N. E. D., S. B. B.] and The Brady Urological Institute [D. F. J., W. B. I.], Johns Hopkins University Medical Center, Baltimore, Maryland 21231

Expression of the Ca2+-dependent, homotypic cell:cell adhesion molecule, E-cadherin (E-cad), suppresses tumor cell invasion and metastasis in experimental tumor models. Decreased E-cad expression is common in poorly differentiated, advanced-stage carcinomas. These data implicate E-cad as an "invasion suppressor" gene. The mechanism by which E-cad is silenced in advanced stage carcinomas is unclear. In this report, we show that: (a) the 5' CpG island of E-cad is densely methylated in E-cad-negative breast and prostate carcinoma cell lines and primary breast carcinoma tissue but is unmethylated in normal breast tissue; (b) treatment with the demethylating agent, 5-aza-2'-deoxycytidine, partially restores E-cad RNA and protein levels in E-cad-negative breast and prostate carcinoma cell lines; and (c) an E-cad promoter/CAT construct is expressed in both E-cad-positive and -negative breast and prostate carcinoma cell lines, indicating that these cells have the active transcriptional machinery necessary for E-cad gene expression. Our data demonstrate that frequent loss of E-cad expression in human breast and prostate carcinomas results from hypermethylation of the E-cad promoter region.

1 This work was supported by National Cancer Institute Grants CA43318 (to J. R. G., J. G. H., H. C., and S. B. B.) and DK49043 (to R. X. and P. M. P.) and a grant from the Susan G. Komen Foundation (to R. G. L.).

2 To whom requests for reprints should be addressed, at The Johns Hopkins University Oncology Center, 424 North Bond Street, Baltimore, MD 21231. Phone: (410) 955-8506; Fax: (410) 614-9884.

Received 8/15/95. Accepted 10/ 2/95.




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