PMID- 12919105 OWN - NLM STAT- MEDLINE DCOM- 20040415 LR - 20071114 IS - 0301-4681 (Print) IS - 0301-4681 (Linking) VI - 71 IP - 6 DP - 2003 Aug TI - Inappropriate P-cadherin expression in the mouse mammary epithelium is compatible with normal mammary gland function. PG - 361-73 AB - Cadherins comprise a family of cell-cell adhesion proteins critical to the architecture and function of tissues. Expression of family members E-, N-, and P-cadherin is regulated in a spatial and temporal fashion in the developing and adult organism. Using in vivo and in vitro experimental systems, perturbation of cadherin expression by genetic deletion, overexpression, mutant dominant-negative constructs, and, to a lesser degree, expression of an inappropriate cadherin have all been shown to alter embryogenesis, tissue architecture, and cell behavior. Here we studied how expression of an inappropriate cadherin affects the adult mouse mammary gland. Human P-cadherin was expressed in mammary epithelial cells under control of the mouse mammary tumor virus (MMTV) promoter, and the effect on mammary gland behavior was studied. Typically, E-cadherin is expressed by mammary epithelial cells, whereas P-cadherin is found in myoepithelial cells and cap cells of the ductal terminal end bud. However, breast cancers frequently express P-cadherin, even though they are thought to arise from epithelial cells, and it is a marker of poor prognosis. We developed two independent transgenic mouse lines that exhibited high levels of P-cadherin protein expression in the mammary epithelium. P-cadherin was detected in most, but not all, luminal epithelial cells, and was appropriately localized to cell-cell borders. It was detected in the mammary glands of virgin, pregnant, lactating, post-lactation, and aged parous female mice. Despite the robust and widespread expression of an inappropriate cadherin, no effect was observed on mammary gland morphogenesis, architecture, lactation, or involution in transgenic mice compared to wild-type mice. No mammary tumors formed spontaneously in either wild-type or transgenic mice. Moreover, mammary tumors induced by the neu oncogene, which was introduced by a breeding strategy, showed no differences between mice with or without hP-cadherin. Surprisingly, however, none of the tumors expressed hP-cadherin protein. Together, our studies show no apparent effect on adult mammary gland or tumor behavior by inappropriate expression of P-cadherin in normal mammary epithelial cells. FAU - Radice, Glenn L AU - Radice GL AD - Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. FAU - Sauer, Christa L AU - Sauer CL FAU - Kostetskii, Igor AU - Kostetskii I FAU - Peralta Soler, Alejandro AU - Peralta Soler A FAU - Knudsen, Karen A AU - Knudsen KA LA - eng GR - CA87261/CA/NCI NIH HHS/United States GR - GM61702/GM/NIGMS NIH HHS/United States GR - R01 GM061702-04/GM/NIGMS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Differentiation JT - Differentiation; research in biological diversity JID - 0401650 RN - 0 (Cadherins) SB - IM MH - Animals MH - Apoptosis MH - Blotting, Western MH - Cadherins/genetics/*metabolism MH - Epithelial Cells/*metabolism MH - Female MH - Gene Deletion MH - Humans MH - Immunohistochemistry MH - Mammary Glands, Human/cytology/*physiology MH - Mammary Neoplasms, Animal/etiology/pathology MH - Mammary Tumor Virus, Mouse/genetics MH - Mice MH - Mice, Transgenic MH - Pregnancy MH - Time Factors EDAT- 2003/08/16 05:00 MHDA- 2004/04/16 05:00 CRDT- 2003/08/16 05:00 PHST- 2003/08/16 05:00 [pubmed] PHST- 2004/04/16 05:00 [medline] PHST- 2003/08/16 05:00 [entrez] AID - S0301-4681(09)60519-3 [pii] AID - 10.1046/j.1432-0436.2003.7106005.x [doi] PST - ppublish SO - Differentiation. 2003 Aug;71(6):361-73. doi: 10.1046/j.1432-0436.2003.7106005.x.