Human chromosomes 1,4,6, and 9 harbor genes which induce cellular senescence in vitro but a role for their inactivation in human tumors is not established. To investigate this we searched for loss of heterozygosity (LOH) on these chromosomes in keratinocyte cultures obtained from different stages of human squamous cell carcinoma progression. There was consistent LOH between markers D9S171 and D...

Growth/differentiation control of normal epithelial cells has been relatively understudied, because of the complexities involved in their cultivation and characterization. The present review is focused on progress in this area using the mouse primary keratinocyte system. This system reproduces under well defined culture conditions the switch between epithelial cell growth and differentiation wh...

We demonstrate that ablation of OTULIN, a deubiquitinase specifically cleaves linear ubiquitin chains, selectively in keratinocytes, results the appearance inflammatory skin lesions develop into verrucous carcinomas. Genetic TNFR1, knockin expression kinase-inactive RIPK1 or keratinocyte-specific deletion FADD and MLKL completely rescues mice with OTULIN deficiency from dermatitis tumorigenesis...

Kindler syndrome (KS) is an autosomal recessive blistering skin disease resulting from pathogenic mutations in FERMT1. This gene encodes kindlin-1, a focal adhesion protein involved in activation of the integrin family of extracellular matrix receptors. Most cases of KS show a marked reduction or complete absence of the kindlin-1 protein in keratinocytes, resulting in defective cell adhesion an...

E2F regulation is essential for normal cell cycle progression. Therefore, it is not surprising that squamous cell carcinoma cell lines (SCC) overexpress E2F1 and exhibit deregulated E2F activity when compared with normal keratinocytes. Indeed, deliberate E2F1 deregulation has been shown to induce hyperplasia and skin tumor formation. In this study, we report on a dual role for E2F as a mediator...