Activation of SRC Tyrosine Kinases Within the Spectrum of Keratinocytic Neoplasia.

Abstract

The Src‐family tyrosine kinases are modulators of growth‐regulatory signals within keratinocytes. The relationship between Src kinases and epidermal neoplasia is unexplored in human biopsies. Keratinocytes express 3 Src kinases: Src, Fyn, Yes. Activation of these kinases corresponds to tyrosine phosphorylation near the active site, tyrosine 416 of human Src. This study compared the levels of total Src‐kinase protein and activated Src kinases within a spectrum of lesions ranging from actinic keratoses (AKs) to squamous cell carcinoma (SCC). An antibody that recognizes an epitope in Src, Fyn, and Yes revealed the total level of Src kinase protein; an antibody specific for the phosphoryated active site tyrosine determined the level of Src kinase activation. The level of Src‐kinase expression and activated Src kinases was evaluated in paraffin imbedded sections of AKs, SCC in‐situ (SCIS), and SCC containing adjacent unremarkable epidermis. The total level of Src kinase protein in lesions was similar to unremarkable epidermis. The level of Src kinase activation was elevated within approximately one‐third of AKs and SCIS, but was increased in over 80% of SCCs. These results demonstrate Src kinases are activated in epidermal neoplasia, and that increased Src kinase activity is associated with the transition from SCIS to SCC.