Activated Akt-1 in specific cell populations during multi-stage skin carcinogenesis.

The goal of the present study was to identify specific populations of cells that contain activated Akt-1, as determined by the presence ofphosphorylated Akt at serine 473 (p Akt), during development of skin tumors using a murine multi-stage carcinogenesis model. Nucleated papillomas cells as well as both epidermal and follicular keratinocytes in hyperplastic skin contained increased pAkt compared to skin treated only with acetone or 7, 12 dimethylbenz[a]anthracene (DMBA). Although the numbers of both mast cells and neutrophils were significantly increased in the stroma of papillomas (p<0.0005; p<0.0001, respectively), only mast cells contained pAkt. The amount of total Akt protein was similar regardless of time or treatment group examined. The present results suggest that activation of Akt-1 may provide specific populations of epidermal keratinocytes that develop into skin tumors with the ability to resist terminal differentiation and have enhanced proliferation during multi-stage skin carcinogenesis. In addition, mast cells which contain activated Akt-1 may persist within the stroma of papillomas during skin tumor development and progression through this signaling pathway, thereby contributing to a pro-oxidant and proangiogenic microenvironment.