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Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis
Published on: December 14, 2015
Initiator and promoter induced specific changes in epidermal function and biological potential
Journal of Supramolecular Structure and Cellular Biochemistry
|January 1, 1981
Summary
Mouse epidermal basal cells resist differentiation signals, a key trait in initiated and malignant cells. Tumor promoters cause cell redistribution, potentially leading to tumor formation and progression.
Area of Science:
- Dermatology
- Carcinogenesis
- Cell Biology
Background:
- Mouse epidermal basal cells can be cultured and manipulated using specific calcium concentrations.
- Altering calcium levels induces terminal differentiation in keratinocytes.
- Carcinogenesis initiators create resistant basal cell colonies.
Purpose of the Study:
- To investigate the resistance of initiated epidermal cells to differentiation.
- To explore basal cell responsiveness to phorbol esters and identify subpopulations.
- To model early stages of skin carcinogenesis and tumor promotion.
Main Methods:
- Selective cultivation of mouse epidermal basal cells in varying calcium concentrations.
- Exposure of basal cells to chemical carcinogens and phorbol esters (12-O-tetradecanoylphorbol-13-acetate, TPA).
- Measurement of ornithine decarboxylase (ODC) induction and transglutaminase activity as markers.
Main Results:
- Initiated basal cells resist calcium-induced differentiation, a characteristic shared with malignant cells.
- Basal cells exhibit enhanced ornithine decarboxylase (ODC) induction by TPA (20-fold increase).
- TPA induces differentiation in one basal cell subpopulation while stimulating proliferation in another, demonstrating heterogeneity.
Conclusions:
- Defects in differentiation commitment are crucial in initiated and malignant epidermal cells.
- Epidermal basal cells display heterogeneity in their response to tumor promoters like TPA.
- Tumor promoters may drive clonal expansion of initiated cells, contributing to benign tumor formation and potential malignant progression.
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