Activation of the extracellular signal-regulated kinases signaling pathway in squamous cell carcinoma of the skin.

Activation of the extracellular signal-regulated kinase (ERK) pathway is involved in many human tumors. Little is known about the role of activated ERK1/2 in squamous cell carcinoma (SCC) of the skin. In this study, the expression and distribution of phosphorylated ERK (p-ERK) in normal human skin and SCC with different degrees of differentiation was examined by immunohistochemical analysis using formalin-fixed paraffin embedded sections. PD98059, a specific ERK pathway inhibitor, was used to evaluate the effect a blockade of ERK activation has on the proliferation of a cutaneous SCC cell line (DJM-1) in culture. In this study, p-ERK 1/2 positive staining was observed in all cases of SCC examined but rarely in the control specimens of normal skin. Moreover, the expression of p-ERK1/2 was significantly higher in poorly differentiated SCC in comparison to well-differentiated ones. Expression levels were positively associated with the degree of malignancy and proliferative activity of SCC. In contrast, inhibition of ERK pathway signaling markedly suppressed tumor cell proliferation. These results suggest that ERK1/2 signal pathways play an important role in the proliferation of SCC and that the inhibition of this signal pathway may be effective in the treatment of cutaneous SCC.