The Role of MEK and Antizyme in Keratinocyte Stem Cell Expansion and Differentiation

The study used transgenic mice to investigate the role of MEK and Antizyme (AZ) in skin tumorigenesis and keratinocyte differentiation. Mice overexpressing MEK showed increased epidermal stem cell expansion and decreased keratinocyte differentiation, leading to epidermal hyperplasia and tumor development. However, co-expression of AZ reduced tumor development by decreasing ornithine decarboxylase (ODC) activity, which is linked to polyamine biosynthesis and tumor promotion. AZ expression counteracted MEK-induced effects, normalizing the number of transient amplifying (TA) cells and stem cells, and restoring differentiation marker levels in keratinocytes. The findings suggested that ODC and polyamines were crucial in regulating epidermal stem cell behavior and keratinocyte differentiation.