Constitutive transgene expression of Stem Cell Antigen-1 in the hair follicle alters the sensitivity to tumor formation and progression

Stem Cell Res. 2017 Aug:23:109-118. doi: 10.1016/j.scr.2017.07.002. Epub 2017 Jul 8.

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 and malignant skin development we 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 stem cells contributes at different stages of tumour development. In early stages, overexpression of Sca-1 decreases tumour formation while at later stages overexpression of Sca-1 seems to drive tumours towards malignant progression.

Keywords: Stem Cell Antigen-1; Stem cell markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Antigens, Ly / metabolism*
  • Carcinogenesis / pathology*
  • Clone Cells
  • Colony-Forming Units Assay
  • Disease Progression*
  • Female
  • Hair Follicle / pathology*
  • Integrases / metabolism
  • Membrane Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Morphogenesis
  • Skin / pathology
  • Tetradecanoylphorbol Acetate
  • Transgenes*

Substances

  • Antigens, Ly
  • Ly6a protein, mouse
  • Membrane Proteins
  • 9,10-Dimethyl-1,2-benzanthracene
  • Cre recombinase
  • Integrases
  • Tetradecanoylphorbol Acetate