Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells
To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε transgenic (TG) mice and their wild-type (WT) littermates for (1) the effects of UVR exposures...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Skin Cancer |
| Online Access: | http://dx.doi.org/10.1155/2013/452425 |
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| author | Ashok Singh Anupama Singh Jordan M. Sand Erika Heninger Bilal Bin Hafeez Ajit K. Verma |
| author_facet | Ashok Singh Anupama Singh Jordan M. Sand Erika Heninger Bilal Bin Hafeez Ajit K. Verma |
| author_sort | Ashok Singh |
| collection | DOAJ |
| description | To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε 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 α6-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 PKCε 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, PKCε over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells. |
| format | Article |
| id | doaj-art-2c2c2b20f86d461681e1e518d9837384 |
| institution | Kabale University |
| issn | 2090-2905 2090-2913 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Skin Cancer |
| spelling | doaj-art-2c2c2b20f86d461681e1e518d98373842025-02-03T05:59:01ZengWileyJournal of Skin Cancer2090-29052090-29132013-01-01201310.1155/2013/452425452425Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem CellsAshok Singh0Anupama Singh1Jordan M. Sand2Erika Heninger3Bilal Bin Hafeez4Ajit K. Verma5Department of Human Oncology, Wisconsin Institutes for Medical Research, School of Medicine and Public Health, 1111 Highland Avenue, University of Wisconsin, Madison, WI 53705, USADepartment of Human Oncology, Wisconsin Institutes for Medical Research, School of Medicine and Public Health, 1111 Highland Avenue, University of Wisconsin, Madison, WI 53705, USADepartment of Human Oncology, Wisconsin Institutes for Medical Research, School of Medicine and Public Health, 1111 Highland Avenue, University of Wisconsin, Madison, WI 53705, USAUWCCC Flow Cytometry Core Facility, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USADepartment of Human Oncology, Wisconsin Institutes for Medical Research, School of Medicine and Public Health, 1111 Highland Avenue, University of Wisconsin, Madison, WI 53705, USADepartment of Human Oncology, Wisconsin Institutes for Medical Research, School of Medicine and Public Health, 1111 Highland Avenue, University of Wisconsin, Madison, WI 53705, USATo find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε 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 α6-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 PKCε 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, PKCε over expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells.http://dx.doi.org/10.1155/2013/452425 |
| spellingShingle | Ashok Singh Anupama Singh Jordan M. Sand Erika Heninger Bilal Bin Hafeez Ajit K. Verma Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells Journal of Skin Cancer |
| title | Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells |
| title_full | Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells |
| title_fullStr | Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells |
| title_full_unstemmed | Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells |
| title_short | Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells |
| title_sort | protein kinase cε which is linked to ultraviolet radiation induced development of squamous cell carcinomas stimulates rapid turnover of adult hair follicle stem cells |
| url | http://dx.doi.org/10.1155/2013/452425 |
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