Altered expression of a mouse epidermal cytoskeletal protein is a sensitive marker for proliferation induced by tumor promoters.

Abstract

Treatment of mouse skin with tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA), 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) or 8-methoxypsoralen and ultraviolet light (PUVA) caused a marked decrease in the expression of p48, an acidic epidermal protein. This protein was specifically identified in mouse epidermis and confluent PAM 212 mouse keratinocytes in culture. Extraction of p48 required strong denaturing conditions (greater than 8 M urea) as well as a reducing agent, indicating that this protein was associated with the cytoskeleton. Positive immunoblot staining of p48 with antikeratin monoclonal antibodies following two-dimensional polyacrylamide gel electrophoresis suggested that this protein may be related to the acidic keratins. The sensitivity of this protein to topically applied mitogens and tumor promoters implies that p48 expression is important in normal epidermal cell growth and differentiation.