P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer

David F. Jarrard, Roger Paul, Adrie Van Bokhoven, Son H. Nguyen, G. Steven Bova, Margaret J. Wheelock, Keith R. Johnson, Jack Schalken, Marion Bussemakers, William B. Isaacs

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Abstract

P-Cadherin is a member of the cadherin family of cell surface glycoproteins that mediate Ca2+-dependent cell-cell adhesion and is expressed in a differential fashion in normal epithelial tissues. The expression of P-cadherin in human prostate cancer development has not been investigated previously. By immunohistochemistry, we show that P-cadherin expression is restricted to the cell-cell border of basal epithelial cells in 30 normal prostate samples. This staining is down-regulated in prostatic intraepithelial neoplasia and is absent in all 25 of the well to poorly differentiated prostate cancer specimens analyzed. To examine potential P- cadherin-regulatory elements, we sequenced the 5'-flanking region of this gene. Similar to the mouse gene, the human P-cadherin promoter is TATA-less, contains an Sp-1 binding site and, analogous to the human E-cadherin sequence, demonstrates a GC-rich region characteristic of a CpG island. Cytosine methylation of this region occurs in P-cadherin-negative prostate cancer cell lines but not in cell lines expressing this gene. In vivo, a lack of expression in 12 clinical prostate cancer specimens is not associated with methylation of the P-cadherin promoter. These results demonstrate that the expression of the basal cell marker P-cadherin is lost in prostate cancer development and that in vivo mechanisms other than cytosine methylation regulate this consistent loss of expression.

Original languageEnglish (US)
Pages (from-to)2121-2128
Number of pages8
JournalClinical Cancer Research
Volume3
Issue number11
Publication statusPublished - Nov 1 1997

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jarrard, D. F., Paul, R., Van Bokhoven, A., Nguyen, S. H., Bova, G. S., Wheelock, M. J., ... Isaacs, W. B. (1997). P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer. Clinical Cancer Research, 3(11), 2121-2128.