Modulation of JB6 mouse epidermal cell transformation response by the prostaglandin F2alpha receptor.
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 [(3)H]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.
Weber
Thomas J
TJ
Molecular Biosciences, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
Markillie
Lye M
LM
Chrisler
William B
WB
Vielhauer
George A
GA
Regan
John W
JW
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D004817:Epidermis / Q000473:pathology*; D051379:Mice; D011869:Radioligand Assay; D011982:Receptors, Prostaglandin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor