Expression of bcl-2 antagonist bak in inflammatory and neoplastic skin diseases

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.