Expression of Double-Stranded RNA-Activated Protein Kinase in Keratinocytes and Keratinocytic Neoplasia
| Autor: | Jirô Arata, Keiji Iwatsuki, Wataru Fujimoto, Gen Nakanishi, Michiyo Kuyama |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Keratinocytes
viruses Immunoblotting Gene Expression Antineoplastic Agents Dermatology Biology medicine.disease_cause environment and public health Malignant transformation Interferon-gamma eIF-2 Kinase Proliferating Cell Nuclear Antigen medicine Humans Psoriasis RNA Messenger Protein kinase A Cells Cultured Cell growth virus diseases General Medicine biochemical phenomena metabolism and nutrition Blotting Northern Protein kinase R Molecular biology Proliferating cell nuclear antigen enzymes and coenzymes (carbohydrates) medicine.anatomical_structure Carcinoma Squamous Cell biology.protein Signal transduction Keratinocyte Carcinogenesis |
| Zdroj: | The Journal of Dermatology. 30:579-589 |
| ISSN: | 0385-2407 |
| DOI: | 10.1111/j.1346-8138.2003.tb00439.x |
| Popis: | Double-stranded RNA-activated protein kinase (PKR) is a interferon-induced protein initially known for its inhibitory effects on cellular and viral protein synthesis. In recent studies, PKR has been shown to be an important participant in a broad array of cellular processes, including signal transduction, differentiation, apoptosis, cell growth, and tumorigenesis. The expression of PKR in normal human keratinocytes (NHEK) was examined, and its expression in several skin lesions was compared immunohistochemically with that of proliferating cell nuclear antigen (PCNA). Expression of PKR mRNA was detected in NHEK without IFNgamma treatment; the level of PKR mRNA increased with IFNgamma treatment for two hours. Immunoblot analysis revealed that the monoclonal anti-PKR antibody reacted specifically with a 68kDa PKR protein in extracts from NHEK. Immunohistochemistry revealed that PKR protein was expressed in normal epidermis and mucosa. PKR expression was not restricted only to suprabasal cells but was also observed in basal cells positive for PCNA. In psoriatic plaques, PKR expression was lower in basal and parabasal keratinocytes and comparable in suprabasal keratinocytes to the levels in normal skin. PKR was partially detected in atypical cells in non-invasive keratinocytic neoplasia but was completely absent from undifferentiated tumor cells of squamous cell carcinoma. The present study demonstrated that PKR protein is constitutively expressed in epidermal and epithelial keratinocytes of normal skin and mucosa and indicated that a loss of PKR is not associated with the malignant transformation itself but with the increased cell proliferative activity and the altered differentiation of keratinocytes. |
| Databáze: | OpenAIRE |
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