%0 Journal Article
%T Protein Kinase C¦Å, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells
%A Ashok Singh
%A Anupama Singh
%A Jordan M. Sand
%A Erika Heninger
%A Bilal Bin Hafeez
%A Ajit K. Verma
%J Journal of Skin Cancer
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/452425
%X To find clues about the mechanism by which kinase C epsilon (PKC¦Å) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKC¦Å 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 ¦Á6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8£¿kJ/m2) resulted in an increase in the frequency of double positive HSCs in PKC¦Å TG mice as compared to their WT littermates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2¡ä-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSCs retaining BrdU label was % compared to % 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¦Å over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells. 1. Introduction The multistage model of mouse skin carcinogenesis is a useful system in which biochemical events unique to initiation, promotion, or progression steps of carcinogenesis can be studied and related to cancer formation. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a component of croton oil, is a potent mouse skin tumor promoter [1, 2]. A major breakthrough in understanding the mechanism of TPA tumor promotion has been the identification of protein kinase C (PKC), as its major intracellular receptor [3]. PKC forms part of the signal transduction system involving the turnover of inositol phospholipids and is activated by DAG, which is produced as a consequence of this turnover [3]. PKC represents a family of phospholipid-dependent serine/threonine kinases [3¨C6]. PKC¦Å is among the six PKC isoforms (¦Á, ¦Ä, ¦Å, ¦Ç, ¦Ì, and ) expressed in both mouse and human skin [7]. We have reported that epidermal PKC¦Å levels dictate the susceptibility of PKC¦Å transgenic (TG) mice to the development of squamous cell carcinomas (SCC) elicited either by repeated exposures to ultraviolet radiation (UVR) [8] or initiation with 7, 12-dimethylbenz[a]anthracene (DMBA) and tumor promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) [9]. Histologically, SCC in TG mice, like human SCC, is poorly differentiated
%U http://www.hindawi.com/journals/jsc/2013/452425/