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Regulation of growth and differentiation of human keratinocytes by type beta transforming growth factor and epidermal
1Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Abstract:
The role of type beta transforming growth factor (TGF beta) and epidermal growth factor (EGF) as regulators of the growth and differentiation of cultured human neonatal epidermal cells and squamous carcinoma cells was investigated in postconfluent cultures. Neither cell proliferation nor DNA synthesis was affected by treatment with TGF beta alone; however, EGF significantly stimulated cell growth, and this process was specifically antagonized by TGF beta. In addition, TGF beta inhibited the maturation of human foreskin-derived epidermal cells, as measured by their competence to synthesize involucrin and to form cornified cell envelopes, in a dose-dependent manner. Although treatment with EGF did not affect the maturation of human foreskin-derived epidermal cells, the combination of a low concentration of TGF beta with EGF resulted in significant enhancement of the maturation of these normal keratinocytes. Growth of three of four squamous carcinomas in the presence of EGF was not inhibited by TGF beta. In addition, all four carcinomas were either totally or partially resistant to the induction of maturation by the combination of TGF beta and EGF. This resistance of squamous carcinomas to TGF beta was paralleled by an increased sensitivity to the antikeratinizing effects of EGF. Thus, TGF beta inhibited the mitogenic stimulation of keratinocytes by EGF and induces cell maturation.
Insights
Type beta transforming growth factor (TGF beta) inhibits epidermal growth factor (EGF)-stimulated keratinocyte proliferation but promotes their maturation. Squamous carcinomas show resistance to TGF beta
Area of Science:
- Cell Biology
- Dermatology
- Cancer Research
Background:
- Type beta transforming growth factor (TGF beta) and epidermal growth factor (EGF) are key regulators of skin cell behavior.
- Understanding their roles is crucial for addressing skin growth disorders and cancers.
Purpose of the Study:
- To investigate the regulatory roles of TGF beta and EGF on human epidermal cell growth and differentiation.
- To compare the effects on normal keratinocytes versus squamous carcinoma cells.
Main Methods:
- Utilized postconfluent cultures of human neonatal epidermal cells and squamous carcinoma cells.
- Administered TGF beta and EGF, individually and in combination.
- Assessed cell proliferation, DNA synthesis, and markers of epidermal differentiation (involucrin synthesis, cornified cell envelope formation).
Main Results:
- TGF beta alone did not affect cell proliferation or DNA synthesis.
- EGF stimulated cell growth, an effect antagonized by TGF beta.
- TGF beta inhibited normal keratinocyte maturation in a dose-dependent manner.
- Combined TGF beta and EGF enhanced normal keratinocyte maturation.
- Squamous carcinomas were largely resistant to TGF beta's inhibitory effects on growth and maturation induction by TGF beta and EGF.
Conclusions:
- TGF beta acts as an inhibitor of keratinocyte proliferation stimulated by EGF.
- TGF beta induces keratinocyte maturation, an effect that can be enhanced by EGF in normal cells.
- Squamous carcinoma cells exhibit resistance to TGF beta's regulatory effects, suggesting a role in cancer progression.