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.
Precocious Mammary Gland Development in P-Cadherin–deficient Mice
Address correspondence to Glenn Radice, Department of Obstetrics and Gynecology, Division of Reproductive Biology, University of Pennsylvania, Room 778 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104-6142. Tel.: 215-898-0164. Fax: 215-573-5408. e-mail: [email protected]
1. Abbreviations used in this paper: APC, adenomatous polyposis coli; ECM, extracellular matrix; ES, embryonic stem; HGF/SF, hepatocyte growth factor/scatter factor; HSV, Herpes simplex virus; PCD-1, P-cadherin antibody.
Special thanks to members of the Takeichi and Hynes labs for making this project possible. We thank Dr. Charles Daniel for the polyclonal casein antibody. We thank Nohelia Canales, Jose Carlos de Lima and Keisha Jones for technical assistance.
Glenn L. Radice, M. Celeste Ferreira-Cornwell, Stephen D. Robinson, Helen Rayburn, Lewis A. Chodosh, Masatoshi Takeichi, Richard O. Hynes; Precocious Mammary Gland Development in P-Cadherin–deficient Mice . J Cell Biol 17 November 1997; 139 (4): 1025–1032. doi: https://doi.org/10.1083/jcb.139.4.1025
Download citation file:
Sign in
Client Account
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
Advertisement