Precocious Mammary Gland Development in P-Cadherin–deficient Mice

作者：Glenn L. Radice, M. Celeste Ferreira‐Cornwell, Stephen D. Robinson, Helen Rayburn, Lewis A. Chodosh, Masatoshi Takeichi, Richard O. Hynes · 发表于：The Journal of Cell Biology · 年份：1997 · DOI：10.1083/jcb.139.4.1025 · 被引用次数：258 · 研究领域：Wnt/β-catenin signaling in development and cancer、Cancer-related gene regulation、Cancer Cells and Metastasis

To investigate the functions of P-cadherin in vivo, we have mutated the gene encoding this cell adhesion receptor in mice. In contrast to E- and N-cadherin- deficient mice, mice homozygous for the P-cadherin mutation are viable. Although P-cadherin is expressed at high levels in the placenta, P-cadherin-null females are fertile. P-cadherin expression is localized to the myoepithelial cells surrounding the lumenal epithelial cells of the mammary gland. The role of the myoepithelium as a contractile tissue necessary for milk secretion is clear, but its function in the nonpregnant animal is unknown. The ability of the P-cadherin mutant female to nurse and maintain her litter indicates that the contractile function of the myoepithelium is not dependent on the cell adhesion molecule P-cadherin. The virgin P-cadherin-null females display precocious differentiation of the mammary gland. The alveolar-like buds in virgins resemble the glands of an early pregnant animal morphologically and biochemically (i.e., milk protein synthesis). The P-cadherin mutant mice develop hyperplasia and dysplasia of the mammary epithelium with age. In addition, abnormal lymphocyte infiltration was observed in the mammary glands of the mutant animals. These results indicate that P-cadherin-mediated adhesion and/or signals derived from cell-cell interactions are important determinants in negative growth control in the mammary gland. Furthermore, the loss of P-cadherin from the myoepithelium has uncovered a...