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β-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion
Abstract
We found that cultured human keratinocytes with high proliferative potential, the putative epidermal stem cells, expressed a higher level of noncadherin-associated β- catenin than populations enriched for keratinocytes of lower proliferative potential. To investigate the physiological significance of this, a series of β-catenin constructs was introduced into keratinocytes via retroviral infection. Full-length β-catenin and a mutant containing only nine armadillo repeats had little effect on proliferative potential in culture, the full-length protein being rapidly degraded. However, expression of stabilised, N-terminally truncated β-catenin increased the proportion of putative stem cells to almost 90% of the proliferative population in vitro without inducing malignant transformation, and relieved the differentiation stimulatory effect of overexpressing the E-cadherin cytoplasmic domain. Conversely, β-catenin lacking armadillo repeats acted as a dominant negative mutant and stimulated exit from the stem cell compartment in culture. The positive and negative effects of the β-catenin mutants on proliferative potential were independent of effects on cell-cycle kinetics, overt terminal differentiation or intercellular adhesion, and correlated with stimulation or inhibition of transactivation of a TCF/LEF reporter in basal keratinocytes. We conclude that the elevated level of cytoplasmic β-catenin in those keratinocytes with characteristics of epidermal stem cells contributes to their high proliferative potential.
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Metadata
- Authors
- Zhu, A. J., & Watt, F. M.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1999-05-15
- Volume
- 126
- Issue
- 10
- Pages
- 2285-2298
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2346241491
- Cited by
- 240
- References
- 2
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- closed
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