Premium
Modulation of JB6 mouse epidermal cell transformation response by the prostaglandin F 2α receptor
Author(s) -
Weber Thomas J.,
Markillie Lye M.,
Chrisler William B.,
Vielhauer George A.,
Regan John W.
Publication year - 2002
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10079
Subject(s) - biology , mapk/erk pathway , signal transduction , epidermal growth factor , microbiology and biotechnology , receptor , extracellular , kinase , mitogen activated protein kinase 3 , biochemistry
Prostaglandin F 2α (PGF 2α ) 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 2α 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 2α 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. © 2002 Wiley‐Liss, Inc.