Selective Ablation of Glucocorticoid Receptor in Mouse Keratinocytes Increases Susceptibility to Skin Tumorigenesis

摘要: We recently demonstrated that mice lacking the epidermal glucocorticoid (GC) receptor (GR) (GR knockout (GREKO) mice) have developmental defects and sensitivity to challenge in adulthood. examined susceptibility of GREKO skin chemical carcinogenesis. treated with a low dose 12-dimethylbenz(a) anthracene (DMBA) followed by phorbol 12-myristate 13-acetate (PMA) promotion exhibited earlier papilloma formation higher incidence multiplicity relative control littermates (CO). Augmented proliferation inflammation defective differentiation keratinocytes contributed phenotype, likely through increased AKT STAT3 (signal transducer activator transcription 3) activities. tumors signs early malignization, including delocalized expression laminin A, dermal invasion keratin 5 (K5)–positive cells, K13 expression, focal loss E-cadherin. Cultured were spindle like, E-cadherin upregulation smooth muscle actin (SMA) Snail, suggesting partial epithelial–mesenchymal transition. A high DMBA PMA generated sebaceous adenomas melanocytic foci CO. Importantly, number, growth kinetics, extent both tumor types mice, addition regulating tumorigenesis from lineages, GR is important for cross-talk other cells. Altogether, our data reinforce importance pathogenesis cancer.