Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin.
When surface epithelium was conditionally targeted for ablation of alpha-catenin, hair follicle development was blocked and epidermal morphogenesis was dramatically affected, with defects in adherens junction formation, intercellular adhesion, and epithelial polarity. Differentiation occurred, but epidermis displayed hyperproliferation, suprabasal mitoses, and multinucleated cells. In vitro, alpha-catenin null keratinocytes were poorly contact inhibited and grew rapidly. These differences were not dependent upon intercellular adhesion and were in marked contrast to keratinocytes conditionally null for another essential intercellular adhesion protein, desmoplakin (DP). KO keratinocytes exhibited sustained activation of the Ras-MAPK cascade due to aberrations in growth factor responses. Thus, remarkably, features of precancerous lesions often attributed to defects in cell cycle regulatory genes can be generated by compromising the function of alpha-catenin.
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
V
V
Vasioukhin
C
C
Bauer
L
L
Degenstein
B
B
Wise
E
E
Fuchs
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D051180:Desmoplakins; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000196:embryology / Q000502:physiology*; D005434:Flow Cytometry; D006133:Growth Substances / Q000378:metabolism; D006197:Hair / Q000502:physiology; D018859:Hair Follicle / Q000378:metabolism / Q000502:physiology*; D007365:Intercellular Junctions; D015603:Keratinocytes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008957:Models, Genetic; D010766:Phosphorylation; D011233:Precipitin Tests; D015398:Signal Transduction; D012867:Skin / Q000196:embryology; D012879:Skin Physiological Phenomena; D013997:Time Factors; D051178:alpha Catenin; D018631:ras Proteins / Q000378:metabolism
C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495295:Dsp protein, mouse; D006133:Growth Substances; D051178:alpha Catenin; D018631:ras Proteins