Truncation of the β-catenin binding domain of E-cadherin precedes epithelial apoptosis during prostate and mammary involution

Christopher J. Vallorosi, Kathleen C. Day, Xin Zhao, Michael G. Rashid, Mark A. Rubin, Keith R. Johnson, Margaret J. Wheelock, Mark L. Day

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

A potential target of hormone action during prostate and mammary involution is the intercellular junction of adjacent secretory epithelium. This is supported by the long-standing observation that one of the first visible stages of prostate and mammary involution is the disruption of interepithelial adhesion prior to the onset of apoptosis. In a previous study addressing this aspect of involution, we acquired compelling evidence indicating that the disruption of E-cadherin-dependent adhesion initiates apoptotic programs during prostate and mammary involution. In cultured prostate and mammary epithelial cells, inhibition of E-cadherin-dependent aggregation resulted in cell death following apoptotic stimuli. Loss of cell- cell adhesion in the nonaggregated population appeared to result from the rapid truncation within the cytosolic domain of the mature, 120-kDa species of E-cadherin (E-cad120). Immunoprecipitations from cell culture and involuting mammary gland demonstrated that this truncation removed the β- catenin binding domain from the cytoplasmic tail of E-cadherin, resulting in a non-β-catenin binding, membrane-bound 97-kDa species (E-cad97) and a free cytoplasmic 35-kDa form (E-cad35) that is bound to β-catenin. Examination of E-cadherin expression and cellular distribution during prostate and mammary involution revealed a dramatic reduction in junctional membrane staining that correlated with a similar reduction in E-cad120 and accumulation of E-cad97 and E-cad35. The observation that E-cadherin was truncated during involution suggested that hormone depletion activated the same apoptotic pathway in vivo as observed in vitro. Based on these findings, we hypothesize that truncation of E-cadherin results in the loss of β- catenin binding and cellular dissociation that may signal epithelial apoptosis during prostate and mammary involution. Thus, E-cadherin may be central to homeostatic regulation in these tissues by coordinating adhesion- dependent survival and dissociation-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)3328-3334
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number5
DOIs
StatePublished - Feb 4 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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