title: Protein Kinase C ε , Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells.
abstract: To find clues about the mechanism by which kinase C epsilon (PKC ε ) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKC ε transgenic (TG) mice and their wild-type (WT) littermates for (1) the effects of UVR exposures on percent of putative hair follicle stem cells (HSCs) and (2) HSCs proliferation. The percent of double HSCs (CD34+ and α 6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8 kJ/m(2)) resulted in an increase in the frequency of double positive HSCs in PKC ε TG mice as compared to their WT littermates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2'-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSCs retaining BrdU label was 28.4 ± 0.6% compared to 4.0 ± 0.06% for the TG mice, an approximately 7-fold decrease. A comparison of gene expression profiles of FACS sorted double positive HSCs showed increased expression of Pes1, Rad21, Tfdp1 and Cks1b genes in TG mice compared to WT mice. Also, PKC ε over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells.
authors.affiliation: Department of Human Oncology, Wisconsin Institutes for Medical Research, School of Medicine and Public Health, 1111 Highland Avenue, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Singh
authors.forename: Anupama
authors.initials: A
authors.lastname: Singh
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Sand
authors.forename: Erika
authors.initials: E
authors.lastname: Heninger
authors.forename: Bilal Bin
authors.initials: BB
authors.lastname: Hafeez
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Verma