PNNL

Abstract

Prostaglandin F2alpha(PGF2alpha) modulates clonal selection processes in the mouse skin model of carcinogenesis. In this study we investigated whether JB6 mouse epidermal cells expressed a functional PGF2alpha receptor (FP) coupled with a cell-transformation response. Treatment of JB6 cells with an FP aonist (fluprostenol) potently (pM-nM) increased anchorage-dependent and anchorage-independent growth. Inositol phospholipid accumulation and extracellular signal-regulated kinase (Erk) activity were increased in cells treated with FP agonists, consistent with established FP-related signal transduction. FP mRNA was detected by reverse transcription-polymerase chain reaction, and the average specific [3H}PGF2alpha binding was 8.25+ or - 0.95 fmol/mg protein. Erk activity and colongy size were increased by cotreatment of JB6 cells with epidermal growth factor (EGF) and fluprostenol to a greater extent than with either treatment alone, whereas the cotreatment effect on colony number appeared to be simply additive. Collectively, our data indicted th JB6 cells expressed a functional FP coupled with transformation-related signal transduction and the regulation of clonal selection processes. Erk activity appears to be a convergence point in the EGF and FP pathways. The data raise the possibility that the FP contributes to clonal selection processes but probably plays a more important role as a response modifier.