P-Cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer.
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.
Jarrard
D F
DF
Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
Paul
R
R
van Bokhoven
A
A
Nguyen
S H
SH
Bova
G S
GS
Wheelock
M J
MJ
Johnson
K R
KR
Schalken
J
J
Bussemakers
M
M
Isaacs
W B
WB
D000818:Animals; D001482:Base Composition; D001665:Binding Sites; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000032:analysis; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D015820:Cadherins; D015226:Dinucleoside Phosphates; D016329:Sp1 Transcription Factor; C015772:CpG dinucleotide