Expression of the cytoplasmic domain of E-cadherin induces precocious mammary epithelial alveolar formation and affects cell polarity and cell-matrixintegrity

Cadherins are cell adhesion molecules involved in cell-cell adhesion, signa lling, and cellular proliferation and differentiation. E-cadherin is requir ed for the formation of epithelium in vivo. We investigated the contributio n of the cytoplasmic domain of E-cadherin to adhesion, signalling, and diff erentiation during murine mammary gland development, by in vivo expression of a gene encoding a truncated form of E-cadherin lacking the extracellular domain. The expression of this gene in mammary epithelial cells during pre gnancy induced precocious lobular epithelial morphogenesis associated with morphological differentiation and the early synthesis of various molecules (advanced milk fat globule appearance and milk protein production). After d elivery, when a fully differentiated and secretory epithelium is required f or lactation, the cytoplasmic domain of E-cadherin had a dominant negative effect on cell-cell adhesion and affected the structure and function of the epithelium. This also led to the partial loss of epithelial polarisation a nd changes in the basement membrane, both important in malignancy. Thus, th e cytoplasmic domain of E-cadherin induces epithelial morphogenesis, but al so alters the cohesiveness of the fully differentiated epithelium. (C) 1999 Academic Press.