Decreased Srcasm expression in hyperproliferative cutaneous lesions

Abstract

Src-family tyrosine kinases (SFKs) are signaling proteins that regulate keratinocyte proliferation and differentiation. Src-activating and signaling molecule (Srcasm) is a recently identified molecule that downregulates SFK activity and promotes keratinocyte differentiation. To determine if Srcasm expression correlates with keratinocyte differentiation, we characterized the level of Srcasm expression in some cutaneous lesions that exhibit increased keratinocyte proliferation. Formalin-fixed sections of randomly selected seborrheic keratoses (SKs) and basal cell carcinomas (BCCs) were analyzed for Srcasm and Ki-67 immunohistochemical staining. Anti-Srcasm and anti-Ki-67 stainings were performed in parallel. All SKs displayed decreased Srcasm staining in areas comprised of basaloid keratinocytes that exhibited an increased Ki-67 index. Higher Srcasm staining levels were detected near pseudohorn cysts where keratinocytes exhibited a lower Ki-67 index. All multicentric and nodular BCCs displayed a prominent loss of Srcasm staining in association with a marked increase in Ki-67 staining. Our results support the hypothesis that Srcasm protein levels are decreased in the hyperproliferative keratinocytes found in SKs and BCCs. Increased Srcasm protein levels are detected in keratinocytes undergoing differentiation. Decreased Srcasm levels may be part of the pathophysiologic mechanism in cutaneous lesions, exhibiting keratinocyte hyperproliferation.