Figure 1.

A KLF4 transgenic mouse model of SCC shows progression to maturation-independnet, constitutive nuclear staining of KLF4, as seen in human skin tumors (Chen, Y.J. et al., this issue). KLF4 was induced in the skin of transgenic mice by administration of doxycycline for 14 days, using a keratin 14 (K14) promoter-dependent expression strategy¹⁰. Skin sections were analyzed by immunostaining, showing that all the epidermal cell layers had become K14-positive. Even though KLF4 transcription is driven by doxycycline in all K14-positive cell layers, only low level KLF4 is detected in the basal, PCNA-positive, epidermal cells of hyperplastic skin (upper panels, see open arrowheads). This result suggests that restriction of KLF4 expression to post-mitotic cells is, at least in part, a post-transcriptional effect. This restriction is lost during tumor progression, as dysplastic skin shows frequent basal expresssion of nuclear KLF4 (lower panels). Insets show the cell-type specific staining at increased magnification. Arrows indicate the demo-epidermal junction, and open arrowheads indicate examples of KLF4-positive, basal keratinocytes. Adapted from reference ¹⁰. Scale bars 100µ (upper panels) or 50µ (lower panles).