Journal
MOLECULAR CARCINOGENESIS
Volume 35, Issue 4, Pages 163-172Publisher
WILEY
DOI: 10.1002/mc.10079
Keywords
cyclooxygenase; epidermal; extracellular signal-regulated kinase; convergence
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Prostaglandin F-2alpha (PGF(2alpha)) modulates clonal selection processes in the mouse skin model of carcinogenesis. In this study we investigated whether JB6 mouse epidermal cells expressed a functional PGF(2alpha) receptor (FP) coupled with a cell-transformation response. Treatment of JB6 cells with an FP agonist (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 [H-3]PGF(2alpha) binding was 8.25 +/- 0.95 fmol/mg protein. Erk activity and colony 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 indicated that 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. (C) 2002 Wiley-Liss, Inc.
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