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

被引:85
作者
Vallorosi, CJ
Day, KC
Zhao, X
Rashid, MG
Rubin, MA
Johnson, KR
Wheelock, MJ
Day, ML
机构
[1] Univ Michigan, Dept Surg, Div Urol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[4] Univ Toledo, Dept Biol, Toledo, OH 43606 USA
关键词
D O I
10.1074/jbc.275.5.3328
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-cad(120)). Immunoprecipitations from cell culture and involuting mammary gland demonstrated that this truncation removed the beta-catenin binding domain from the cytoplasmic tail of E-cadherin, resulting in a non beta-catenin binding, membrane-bound 97-kDa species (E-cad(97)) and a free cytoplasmic 35-kDa form (E-cad(34)) that is bound to beta-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-cad(120) and accumulation of E-cad(97) and E-cad(35). 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 beta-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.
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页码:3328 / 3334
页数:7
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