Evidence for a role of mitogen-activated protein kinases in proliferating and differentiating odontogenic epithelia of inflammatory and developmental cysts.

Abstract

The activation of intracellular signaling cascades involving serine/threonine kinases ERK1/2 has been variably reported either to stimulate or inhibit epithelial cell differentiation in response to extracellular signals. The purpose of our study was to determine the distribution of the signaling molecule ERK1 and its activated form pERK1/2 in the epithelial components of developmental and inflammatory odontogenic cysts in relation to parameters of differentiation and proliferation. Thirty samples of dental follicles, dentigerous cysts, and radicular cysts were immunostained with antibodies to ERK1, pERK1/2, and proliferating cell nuclear antigen (a marker for proliferation). The tissues were subclassified according to the pattern of histomorphological differentiation (ie, squamous differentiation) and the proliferation rate of their epithelial components. The significance of differences in the proportion of ERK1- and pERK1/2-expressing cells among the tissue groups was determined by chi-square analysis or Fisher's exact test. ERK1 and pERK1/2 were found to be expressed in a significantly higher proportion of cells with differentiated and highly proliferating epithelial components, as compared with those of nondifferentiated, quiescent epithelial rests. The epithelium of radicular cysts exhibited the highest proportion of pERK1/2-positive cells. In both dentigerous and radicular cyst samples, pERK1/2 expression was significantly higher in the inflamed tissues. These data demonstrate that ERK1 and its active form pERK1/2 are associated with differentiating and actively proliferating epithelia of odontogenic cysts, and are consistent with pERK1/2 involvement in the activation of odontogenic epithelia in response to inflammation.