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Cell Growth & Differentiation Vol. 11, 111-121, February 2000
© 2000 American Association for Cancer Research


Articles

Epidermal Overexpression of Granulocyte-Macrophage Colony-Stimulating Factor Induces Both Keratinocyte Proliferation and Apoptosis1

Kai Breuhahn2, Amrit Mann2, Gabriele Müller, Arnd Wilhelmi, Peter Schirmacher, Alexander Enk and Manfred Blessing3

SFB-432, I. Medical Department [K. B., A. M., M. B.], Department of Dermatology [G. M., A. E.], Boehringer Ingelheim Research Group, SFB-311, I. Medical Department [A. W., M. B.], and Institute of Pathology [P. S.], Johannes Gutenberg University, D-55131 Mainz, Germany

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is released by keratinocytes in sizeable amounts only under pathological conditions, e.g., after topical application of a tumor promoter, in atopic dermatitis (AD), and after wounding. To study the biological function of this cytokine release, we generated transgenic mice that constitutively overexpress GM-CSF in the epidermis. An increase in the numbers of mast cells and Langerhans cells (LCs) in transgenics versus nontransgenic controls was observed but no severe inflammation. This is consistent with a central role of this cytokine in the development and maturation of LCs. Mitotic activity in the epidermis of transgenic mice was elevated, but epidermal thickness and differentiation were normal. Homeostasis is maintained by an increase of apoptosis in the epidermis. We describe the differential expression of regulators of apoptosis and discuss a potential mechanism for this novel proapoptotic activity of GM-CSF on keratinocytes. Both stimulation of proliferation and promotion of apoptosis are of great relevance to tumorigenesis. The latter may be a means of removing damaged cells after genotoxic stress or injury.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2000 by the American Association of Cancer Research.