Aberrant expression during two‐stage mouse skin carcinogenesis of a type 147‐kDa keratin, k13, normally associated with terminal differentiation of internal stratified epithelia

Abstract

Specific keratin cDNA probes and monospecific antikeratin antisera were used to analyze mouse epidermis and epidermal tumors for the expression of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. We demonstrated that this keratin was virtually absent from the entire body epidermis at various stages of development. Also, it was not detected in various forms of acute and chronic epidermal hyperproliferation or in epidermal cells cultured under conditions that favored either cell proliferation or in vitro differentiation. In contrast, K13 was consistently expressed in squamous cell carcinomas of the skin induced by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate (TPA), whereas papillomas obtained by the same two-stage protocol were distinctly heterogeneous with regard to the expression of this keratin. These findings were true for two different strains of mice (NMRI and Sencar). Papillomas collected from Sencar mice after 12 wk or from NMRI mice after 15 wk of promotion with TPA were either negative for K13 or elicited variable amounts of this keratin. In all cases of positive expression of K13 in tumors, as in normal stratified internal epithelia, both the keratin protein and its mRNA invariably occurred in the differentiating cell compartments. In contrast to what we found in internal stratified epithelia, however, K13 was expressed without its commonly encountered type II 57-kDa partner, K4. Papillomas negative for the K13 protein were also devoid of K13 transcripts. This indicates that the aberrant K13 expression in tumors is regulated at the level of transcription. Our results suggest that K13 may provide a marker for malignant conversion in the mouse two-stage skin carcinogenesis model and may be especially suited for studies of gene expression regulation.

Smad3 Knockout Mice Exhibit a Resistance to Skin Chemical Carcinogenesis

“…2). In contrast, strongly positive immunofluorescence staining for K13, a malignancy marker in squamous epithelia (32), was observed in tumors classified as SCCs from both Smad3 ϩ/ϩ and Smad3 ϩ/Ϫ mice, but not in tumors from Smad3 Ϫ/Ϫ mice ( Fig. 2), further confirming that the tumors from the Smad3 Ϫ/Ϫ mice were benign papillomas.…”

Expression of a truncated form of hHb1 hair keratin in human breast carcinomas

“…normally associated with the terminal differentiation of internal stratified epithelia. has been reported in mouse skin tumours (Nischt et al 1988). …”

VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development

“…As expected, expression of the hyperproliferation-associated keratin K6 apperared highly induced in a continuous pattern in both transgenic and control tumors (Figure 7a and b). Aberrant expression of keratin K13, a marker for progression in mouse skin carcinogenesis (Nischt et al, 1988;Gimenez-Conti et al, 1990), was observed in both types of tumors. At 6 weeks, most transgenic tumors show continuous K13 expression, while control tumors show focal staining (Figure 7c and d).…”