Growth factor and proto-oncogene expression in psoriasis

Abstract

The expression of several proto-oncogenes and growth factors was analyzed in normal skin and and psoriatic lesions by RNA blot hybridization. Isolation of intact RNA from frozen biopsy samples required immediate exposure to denaturants during tissue homogenization. Lipocortin II and cyclophilin transcripts were used as internal controls. These transcripts were abundant and slightly but significantly elevated in psoriatic lesions. When results were normalized according to these reference transcripts, there was no increase in the expression of c-myc, c-Ha-ras, c-erbB (EGF receptor), c-jun, or transforming growth factor-β (TGF-β) transcripts in psoriatic lesions, and lesional c-fos transcripts were decreased relative to normal skin. In contrast, expression of TGF-α mRNA transcripts were markedly increased in psoriatic lesions even after normlization. Placement of normal or psoriatic tissue in organ culture for 2 to 4 h resulted in strong induction of c-fos, c-jun, and myc transcripts, but not of the the other genes studied. Thus, overexpression of proto-oncogenes may be more characteristic of the epidermal response to acute injury than of the steady-state hyperplasia characteristic of psoriasis. Interferon-γ (IFN-γ) increased TGF-α mRNA levels in cultured human KC at long time intervals (24-48 h). However, of various cytokines tested, only EGF and TGF-α induced TGF-α mRNA after short time intervals (2-4 h). These results as well as the selective overabundance of TGF-α mRNA in psoriatic lesions among various cytokines tested suggest that activation of the EGF receptor tyrosine kinase by TGF-α in important in the pathogenesis of psoriatic epidermal hyperplasia. © 1990.