Basic fibroblast growth factor regulates persistent ERK oscillations in premalignant but not malignant JB6 cells.
The regulation of extracellular signal-regulated kinase (ERK) oscillations in the context of wound healing and carcinogenesis have been investigated in premalignant and malignant JB6 mouse epidermal cells stimulated with basic fibroblast growth factor (bFGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA). In premalignant JB6 cells, bFGF stimulation (1) increases cellular phospho-ERK and phospho-c-Jun levels, (2) increases serum-dependent cell proliferation, (3) induces an apparent epithelial-to-mesenchymal transition, and (4) induces the persistent nuclear-cytosolic oscillation of an ERK1-green fluorescent protein (ERK1-GFP) chimera. In contrast, TPA induces persistent activation of ERK in the absence of oscillations and does not induce efficient migration. Treatment of malignant or transformed JB6 cells with bFGF is associated with a transient nuclear translocation of ERK1-GFP but not oscillations or efficient cell migration. Our data suggest that bFGF regulates ERK oscillations in premalignant but not malignant JB6 cells.
Weber
Thomas J
TJ
Cell Biology and Biochemistry Group, Fundamental Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA. Thomas.Weber@pnl.gov
Shankaran
Harish
H
Wiley
H Steven
HS
Opresko
Lee K
LK
Chrisler
William B
WB
Quesenberry
Ryan D
RD
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014945:Wound Healing / Q000502:physiology
D002273:Carcinogens; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate