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Truncated E‐cadherin potentiates cell death in prostate epithelial cells
Author(s) -
RiosDoria Jonathan,
Day Mark L.
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20179
Subject(s) - cadherin , prostate , epithelium , programmed cell death , medicine , prostate cancer , cancer research , prostate disease , cell , apoptosis , biology , pathology , cancer , genetics
BACKGROUND E‐cadherin, a fundamental component of the adherens junction, is known to mediate aggregation‐dependent cell survival. We have previously identified a novel, calpain‐dependent proteolytic cleavage of E‐cadherin that resulted in the generation of a stable 100‐kDa E‐cadherin fragment (E‐cad 100 ) in prostate epithelial cells in response to cell death stimuli. We postulated that the E‐cad 100 fragment may play a role in abrogating survival of LNCaP cells following induction of apoptosis. METHODS Wild‐type E‐cadherin and E‐cad 100 were engineered, tagged with GFP, and stably expressed in LNCaP cells. These cell lines were characterized for E‐cadherin‐GFP/β‐catenin interactions, endogenous E‐cadherin and β‐catenin expression, and sensitivity to apoptosis induced by PKC activation. RESULTS E‐cad 100 ‐GFP demonstrated a punctuate expression pattern, in contrast to E‐cad 120 ‐GFP, which was membrane‐localized. E‐cad 100 ‐GFP, unlike E‐cad 120 ‐GFP, failed to bind to and co‐localize with β‐catenin. Transient or stable overexpression of E‐cad 100 resulted in the downregulation of endogenous E‐cadherin expression at the cell membrane. Activation of PKC in LNCaP cells which overexpressed E‐cad 100 potentiated cell death. CONCLUSIONS Truncated E‐cadherin may play a role in the regulation of endogenous E‐cadherin expression and epithelial cell survival. © 2004 Wiley‐Liss, Inc.