Chronic expression of p16^INK4a in the epidermis induces Wnt-mediated hyperplasia and promotes tumor initiation.

ABSTRACT: p16^INK4a (CDKN2A) is a central tumor suppressor, which induces cell-cycle arrest and senescence. Cells expressing p16^INK4a accumulate in aging tissues and appear in premalignant lesions, yet their physiologic effects are poorly understood. We found that prolonged expression of transgenic p16^INK4a in the mouse epidermis induces hyperplasia and dysplasia, involving high proliferation rates of keratinocytes not expressing the transgene. Continuous p16^INK4a expression increases the number of epidermal papillomas formed after carcinogen treatment. Wnt-pathway ligands and targets are activated upon prolonged p16^INK4a expression, and Wnt inhibition suppresses p16^INK4a-induced hyperplasia. Senolytic treatment reduces p16^INK4a</

SUBMITTER: Azazmeh N 

PROVIDER: S-EPMC7264228 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature