Constitutive transgene expression of Stem Cell Antigen-1 in the hair follicle alters the sensitivity to tumor formation and progression
Authors
Rikke Christensen, David M. Owens, Annette C. Füchtbauer, Anders Gunnarsson, Mette Ramsing, Ernst-Martin Füchtbauer, Uffe Birk Jensen
Institution
Aarhus University Hospital
Country
Denmark
Year
2017
Journal
Stem Cell Research
Abstract
The cell surface protein Stem Cell Antigen-1 (Sca-1) marks stem or progenitor cells in several murine tissues and
is normally upregulated during cancer development. Although the specific function of Sca-1 remains unknown,
Sca-1 seems to play a role in proliferation, differentiation and cell migration in a number of tissues. In the skin
epithelium, Sca-1 is highly expressed in the interfollicular epidermis but is absent in most compartments of
the hair follicle; however, the function of Sca-1 in the skin has not been investigated. To explore the role of
Sca-1 in normal andmalignant skin developmentwe generated transgenic mice that express Sca-1 in the hair follicle
stem cells that are normally Sca-1 negative. Development of hair follicles and interfollicular epidermis appeared
normal in Sca-1 mutant mice; however, follicular induction of Sca-1 expression in bulge region and
isthmus stem cells reduced the overall yield of papillomas in a chemical carcinogenesis protocol. Despite that
fewer papillomas developed in transgenic mice a higher proportion of the papillomas underwent malignant conversion.
These findings suggest that overexpression of Sca-1 in the hair follicle stemcells contributes at different
stages of tumour development. In early stages, overexpression of Sca-1 decreases tumour formationwhile at later
stages overexpression of Sca-1 seems to drive tumours towards malignant progression