Arch Dermatol Res (1991) 283:113-118 Archives of N@ @ I?@Ifl 9 Springer-Verlag1991 The expression of skin-specific gene K51 in the epidermal layer of human skin and in basal cell carcinoma cells V. R. Babaev 1, M. E. Belowa 2, A. V. Tkachenko 2, E. M. Tararak 1, I. A. Kazantseva 3, and I. M. Chumakov 2 1 Cardiology Research Center, USSR Academyof Medical Sciences, Moscow, USSR 2 V. A. EngelhardtInstitute of Molecular Biology, Academy of Sciencesof the USSR, Moscow, USSR 3 HumanMorphologyInstitute, USSR Academy of Medical Sciences,Moscow,USSR Received April 28, 1990 Summary. Gene K51 probe isolated previously from the rat genomic library has been used to study the expression of its human counterpart by in situ hybridization and Northern blot analysis. A polyA-containing transcript of human gene K51 of 3 kb size has been detected in embryonic skin. The gene is also expressed in the epidermis of newborn humans and adults, but not in the adjacent mesenchymal tissues. Immunostaining with keratin antisera revealed predomi- nantly earlier stage expression of K51 than cytokeratin markers. Sebaceous and sweat glands also contain cells expressing K51 gene. K51 expression was found in the cells of eight individual basal cell carcinomas tested, with the level of expression lower than in keratinocytes from normal human epidermis. We propose that K51 gene expression could serve as a convenient marker for the study of the process of skin keratinocyte development and the changes in this process associated with skin cancers and dysplasia. Key words: Epidermis - Basal cell carcinoma - In situ hybridization Skin presents a very attractive model to study stem cell proliferation and development [7, 10]. Several genes, ex- pressed during the terminal differentiation process, have been isolated [5, 9]. Some of them can serve as specific markers for the identification of certain stages leading to the formation of stratum corneum and to stem cell re- newal [19]. These markers could also play a role in the identification of precursor cells for different types of skin cancer. Eventually that could result in a more systematic tumour classification and rational treatment procedures. Some of these tumours, such as basal cell carcinoma (BCC) [6], present an attractive model for the study of the balance between keratinocyte proliferation and differ- entiation. BCCs are commonly encountered cutaneous, Offprint requests to: I. M. Chumakov epithelial tumours that are locally aggressive, but with little metastatic potential [14]. They are thought to arise from either altered basal cells or primordia of adnexal structures [8]. Despite our familiarity with BCCs as a clinical entity, our knowledge of defects leading to their formation is incomplete. We have previously isolated from the rat genomic library and sequenced the genomic fragment containing the new gene K51 [4]. Part of it contains the open reading frame coding for the peptide resembling the hyper- variable domain of cytokeratins, and abundant in cysteine residues [16]. This hypothetical protein is not present in the latest versions of sequence data banks. It contains several types of repeats, with the most character- istic motif being (Gly)2(Ser)2Cys(Gly)3 which is present nine times. Homology can also be demonstrated at the DNA level (65% over more than 200 bp distance). We have not been able to demonstrate the sequence homol- ogy with other parts of either type I or type II keratin genes. Short regions of homology with some other pro- teins, including the ATP-binding domain of oncoprotein mos, were found during sequence analysis, but are only marginally significant. This genomic clone was used as a probe to study the expression of K51 in mouse and rat tissues [18]. The transcription in this system is very stage- and tissue-specific. K5I abruptly starts to be expressed in the skin of mouse embryo 3 days before birth, the transcription reaching a maximum in the newborn in the layer just below the stratum corneum, and being greatly reduced at the time of hair growth and in adult epidermis. Such peculiar stage- and tissue-specificity led us to propose that K51 expression could serve as a convenient marker to monitor normal and aberrant human skin development. The combination of in situ hybridization, Northern RNA analysis and immunostaining-with kera- tin antibodies shows that K51 is expressed in human skin and BCCs, and its expression occurs more in the basal layers of the epidermis than the expression of the bulk of keratins. The transcription of K51 is reduced in basal cell tumours, where the balance between proliferation and differentiation is changed.