beta-Catenin regulates P-cadherin expression in mammary basal epithelial cells.
P-cadherin expression is restricted to the basal layer of stratified epithelia including that of the mammary gland. Although evidence for an important role of P-cadherin in mammary morphogenesis and tumorigenesis is increasing, the mechanisms that regulate its expression are poorly understood. We show that in basal mammary epithelial cells, beta-catenin is associated with the P-cadherin promoter and activates its expression independently of LEF/TCF in a cell-type specific manner. Down-regulation of endogenous beta-catenin levels by RNA interference technique inhibited P-cadherin promoter activity. In vivo, in skin and mammary gland of mutant mice, activation of beta-catenin signalling correlates with up-regulation of P-cadherin expression. These data suggest that beta-catenin-dependent modulation of P-cadherin expression can contribute to the establishment of the basal phenotype.
Faraldo
Marisa M
MM
UMR 144, CNRS-Institut Curie, Section de Recherche, 26, rue d'Ulm, 75248 Paris, Cedex 05, France. faraldo@curie.fr
Teulière
Jérôme
J
Deugnier
Marie-Ange
MA
Birchmeier
Walter
W
Huelsken
Joerg
J
Thiery
Jean Paul
JP
Cano
Amparo
A
Glukhova
Marina A
MA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D017931:DNA Primers; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051176:beta Catenin