Prostaglandin-H-synthase isozyme expression in normal and neoplastic human skin

Expression of prostaglandin-H-synthase (PGHS) isozymes was analyzed in 50 biopsies of normal human skin and of pre-malignant and malignant skin lesions, by means of quantitative RT-PCR, immunoprecipitation and Western blotting, as well as immunohistochemistry. Normal skin constitutively expressed PG...

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Main Authors: Müller-Decker, Karin (Author) , Krieg, Peter (Author) , Bayerl, Christiane (Author) , Marks, Friedrich (Author) , Fürstenberger, Gerhard (Author)
Format: Article (Journal)
Language:English
Published: 10 November 1999
In: International journal of cancer
Year: 1999, Volume: 82, Issue: 5, Pages: 648-656
ISSN:1097-0215
DOI:https://doi.org/10.1002/(SICI)1097-0215(19990827)82:5<648::AID-IJC6>3.0.CO;2-D
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/(SICI)1097-0215(19990827)82:5<648::AID-IJC6>3.0.CO;2-D
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291097-0215%2819990827%2982%3A5%3C648%3A%3AAID-IJC6%3E3.0.CO%3B2-D
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Author Notes:Karin Müller‐Decker, Günther Reinerth, Peter Krieg, Regina Zimmermann, Helmut Heise, Christiane Bayerl, Friedrich Marks and Gerhard Fürstenberger
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Summary:Expression of prostaglandin-H-synthase (PGHS) isozymes was analyzed in 50 biopsies of normal human skin and of pre-malignant and malignant skin lesions, by means of quantitative RT-PCR, immunoprecipitation and Western blotting, as well as immunohistochemistry. Normal skin constitutively expressed PGHS-1 in all cell layers of the epidermis, in endothelial cells of small blood vessels and in sweat-gland epithelium. PGHS-2 expression was very low and restricted to a few keratinocytes of the interfollicular and follicular epidermis. Steady-state concentrations of PGHS-1 and PGHS-2 mRNA were similar in normal skin and in basal-cell carcinomas, but PGHS-1 mRNA was reduced and PGHS-2 mRNA was elevated in actinic keratoses, squamous-cell carcinomas and keratoacanthomas. PGHS-1 protein was detected in all tumor biopsies, being occasionally increased in basal-cell carcinomas. High amounts of PGHS-2 protein were found in actinic keratoses, squamous-cell carcinomas and keratoacanthomas, but not in basal-cell carcinomas. Four malignant melanomas included in this study contained PGHS-1 but no PGHS-2 protein. Immunohistochemical analysis of the biopsies identified keratinocytes, in addition to cells of inflammatory infiltrates and of dendritic morphology, as the major PGHS-expressing cell types. PGHS-2-specific signals were spread throughout the epidermal part of actinic keratoses and squamous-cell carcinomas. These data suggest that constitutive up-regulation of PGHS-2 expression is a consistent pre-malignant event in squamous-cell cancer development in man, as it is in animal models of skin carcinogenesis. Thus, pre-cancerous lesions such as actinic keratoses present a likely target for chemoprevention of skin cancer by selective PGHS-2 inhibitors.
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Physical Description:Online Resource
ISSN:1097-0215
DOI:https://doi.org/10.1002/(SICI)1097-0215(19990827)82:5<648::AID-IJC6>3.0.CO;2-D