title: Modulation of JB6 mouse epidermal cell transformation response by the prostaglandin F2alpha receptor.
abstract: 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.
authors.affiliation: Molecular Biosciences, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Weber
authors.forename: Lye M
authors.initials: LM
authors.lastname: Markillie
authors.forename: William B
authors.initials: WB
authors.lastname: Chrisler
authors.forename: George A
authors.initials: GA
authors.lastname: Vielhauer
authors.forename: John W
authors.initials: JW
authors.lastname: Regan
mesh_terms: 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
chemical_list: D017931:DNA Primers; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor