Precocious Mammary Gland Development in P-Cadherin–deficient Mice

Abstract

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 novel function for this tissue in maintaining the undifferentiated state of the underlying secretory epithelium.

Nephrin Forms a Complex with Adherens Junction Proteins and CASK in Podocytes and in Madin-Darby Canine Kidney Cells Expressing Nephrin

“…20,38 It is clear from nephrin and CD2AP knockout mice, 39,54 nephrin TRAP mice, 55 and human patients with congenital nephrotic syndrome of the Finnish type 1 that nephrin and CD2AP expression are essential for normal glomerular development and function. Interestingly, P-cadherin knockout mice have no glomerular defects, 56 suggesting either that P-cadherin is not essential or that other members of the cadherin superfamily substitute for P-cadherin in these mice. The pathways by which nephrin influences cell behavior have just begun to be investigated.…”

The Prognostic Significance of P-Cadherin in Infiltrating Ductal Breast Carcinoma

“…P-CD expression is characteristic of the stem cells (cap cells), the precursor of myoepithelial cells, which do not express estrogen receptors and have a high proliferation rate and low frequency of apoptosis (7). In addition, P-CD-deficient mice have anomalous mammary gland development (8).…”

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

“…However, experiments using the mouse as a model system indicate that at the terminal end bud, where the lumen is filled and cell motility and rearrangements are elevated, cell positioning is rarely lost (9,10). Moreover, deletion of key cell-cell adhesion proteins such as E-and P-cadherin has no gross effect on MEP or LEP cell positioning in the developing mouse mammary gland (11,12). This is surprising given the established role of cadherins in guiding cell positioning through cell sorting.…”