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Published on: January 14, 2011
Expression of bcl-2 antagonist bak in inflammatory and neoplastic skin diseases
H Tomková1, W Fujimoto, J Arata
1Department of Dermatology, Okayama University Medical School, Japan.
Abstract:
Bak (bcl-2 homologous antagonist/killer) is a proapoptotic member of the ever-expanding bcl-2 gene family, a recently described category of oncogenes that is critical for the regulation of programmed cell death. We investigated the expression of bak in several inflammatory and neoplastic skin diseases in comparison with normal skin. Immunohistochemical analysis revealed positive bak staining in epidermal keratinocytes of normal skin, with the granular layer being stained slightly more strongly than the basal and spinous layers, and in psoriasis vulgaris, lichen planus, actinic keratosis, keratoacanthoma and squamous cell carcinoma. We demonstrated the expression of bak in the follicular infundibulum in contrast to the outer root sheath of the lower follicle, which showed only negative to weak bak expression. Seventeen of 20 basal cell carcinomas examined showed negative immunostaining for bak, and the remaining three basal cell carcinomas showed only partial weak positivity, mainly in the palisading layers of some tumour formations. Immunoblot analysis using cultured normal human epidermal keratinocytes revealed the presence of bak protein in both undifferentiated and differentiated keratinocytes. The results of our study suggest that the loss of bak expression, in conjunction with the previously reported overexpression of bcl-2, might contribute to the pathogenesis of basal cell carcinoma.
Insights
The proapoptotic protein Bak is expressed in normal skin and various skin diseases. Loss of Bak expression, along with Bcl-2 overexpression, may contribute to basal cell carcinoma development.
Area of Science:
- Dermatology
- Oncology
- Molecular Biology
Background:
- Bak (bcl-2 homologous antagonist/killer) is a proapoptotic protein crucial for regulating programmed cell death.
- The bcl-2 gene family includes oncogenes involved in cell death regulation.
- Understanding Bak expression in skin diseases is important for pathogenesis research.
Purpose of the Study:
- To investigate the expression patterns of Bak in normal skin and various inflammatory and neoplastic skin conditions.
- To compare Bak expression in different skin layers and appendages.
- To explore the potential role of Bak in the pathogenesis of basal cell carcinoma.
Main Methods:
- Immunohistochemical analysis of skin tissue samples.
- Immunoblot analysis of cultured human epidermal keratinocytes.
Main Results:
- Positive Bak staining was observed in epidermal keratinocytes of normal skin and in psoriasis vulgaris, lichen planus, actinic keratosis, keratoacanthoma, and squamous cell carcinoma.
- Bak was expressed in the follicular infundibulum but showed weak or negative expression in the outer root sheath.
- Seventeen of 20 basal cell carcinomas exhibited negative Bak immunostaining, with three showing weak positivity.
Conclusions:
- Bak is expressed in various skin compartments and diseases.
- The loss of Bak expression in basal cell carcinoma, potentially alongside Bcl-2 overexpression, may play a role in its pathogenesis.
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