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

Journal Article · Mon Dec 09 04:00:00 EST 2002 · Molecular Carcinogenesis, 35(4):163-172

DOI:https://doi.org/10.1002/mc.10079· OSTI ID:15003545

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

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 15003545
• Report Number(s): PNNL-SA-38182; KP1102020
• Journal Information: Molecular Carcinogenesis, 35(4):163-172, Journal Name: Molecular Carcinogenesis, 35(4):163-172 Journal Issue: 4 Vol. 35
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARCINOGENESIS
CELL TRANSFORMATIONS
CHAIN REACTIONS
CONVERGENCE
FUNCTIONALS
GROWTH FACTORS
INOSITOL
MODULATION
PHOSPHOLIPIDS
PHOSPHOTRANSFERASES
PROSTAGLANDINS
Prostaglandin
tumor promotion
EGF
REGULATIONS