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Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin.
- Source :
-
Cell [Cell] 2001 Feb 23; Vol. 104 (4), pp. 605-17. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Alleles
Animals
Blotting, Southern
Blotting, Western
Cell Adhesion
Cell Cycle
Cell Division
Cells, Cultured
Cytoskeletal Proteins genetics
Desmoplakins
Electrophoresis, Polyacrylamide Gel
Epithelium embryology
Flow Cytometry
Growth Substances metabolism
Hair physiology
Hair Follicle metabolism
Intercellular Junctions
Keratinocytes metabolism
MAP Kinase Signaling System
Mice
Mice, Knockout
Microscopy, Fluorescence
Mitosis
Models, Genetic
Phosphorylation
Precipitin Tests
Signal Transduction
Skin embryology
Skin Physiological Phenomena
Time Factors
alpha Catenin
ras Proteins metabolism
Cytoskeletal Proteins physiology
Epithelium physiology
Hair Follicle physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0092-8674
- Volume :
- 104
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 11239416
- Full Text :
- https://doi.org/10.1016/s0092-8674(01)00246-x