Modulation of JB6 Mouse Epidermal Cell Transformation Response by the Prostaglandin F2 Alpha Receptor

Journal Article · Sun Dec 01 04:00:00 EST 2002 · Molecular Carcinogenesis

DOI:https://doi.org/10.1002/mc.10079· OSTI ID:860117

Weber, Thomas J; Markillie, Lye MENG; Chrisler, William B; Vielhauer, George A; Regan, John W

Prostaglandin F2a (PGF2a) has been associated with the modulation of clonal selection processes in the mouse skin model of carcinogenesis. We have investigated whether JB6 mouse epidermal cells express a functional PGF2a receptor (FP) coupled to the regulation of anchorage-dependent and -independent growth. Treatment of JB6 cells with a FP receptor ligand (fluprostenol) potently (pM-nM) increased anchorage-dependent and -independent growth, as determined by a battery of in vitro assays. Treatment of JB6 cells with PGF2a and fluprostenol increased inositol phospholipid accumulation and extracellular signal regulated kinase (ERK) activity, consistent with FP receptor-related signaling. FP receptor mRNA was detected by reverse transcription-polymerase chain reaction and a radiolabel binding assay determined the average specific [3H]PGF2a binding to be 8.25 + 0.95 fmol/mg protein. Treatment of cells with fluprostenol as a single exposure resulted in a significant increase in anchorage-dependent and -independent growth in media containing low (0.1-0.5%), but not high (5%) concentrations of fetal bovine serum (FBS). In contrast, treatment of cells with fluprostenol at two day intervals resulted in a more robust growth response under anchorage-dependent conditions only in media containing low FBS concentrations; and under anchorage-independent conditions only in media containing high FBS concentrations. ERK activation and colony size were increased by cotreatment of JB6 cells with EGF and fluprostenol to a greater extent than either treatment alone, while the cotreatment effect on colony number appeared to be simply additive. In summary, FBS concentration and signal oscillation exert pronounced effects on the biological response to a FP receptor agonist. The data raise the possibility that the FP receptor may independently contribute to clonal selection processes, but may play a more important role as a response modifier.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 860117
• Report Number(s): PNWD-SA-5669; KP1102020
• Journal Information: Molecular Carcinogenesis, Journal Name: Molecular Carcinogenesis Journal Issue: 4 Vol. 35
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARCINOGENESIS
CATTLE
CELL TRANSFORMATIONS
CHAIN REACTIONS
FUNCTIONALS
IN VITRO
INOSITOL
MODULATION
OSCILLATIONS
PHOSPHOLIPIDS
PHOSPHOTRANSFERASES
PROSTAGLANDINS
REGULATIONS