Effects of endogenous epidermal growth factor receptor signaling on DNA synthesis and ERK activation in a cytokine-dependent hematopoietic cell line.
Epidermal growth factor (EGF) is commonly thought to affect the proliferation of many cells, especially epithelial cells. Aberrant expression of the receptor for EGF, (EGFR) or members of the EGFR family is often implicated in the etiology of many cancers. Ligation of the EGFR results in the activation of many downstream signaling pathways which have profound effects on cell cycle progression and the prevention of apoptosis. In general, the EGFR is thought to be either not expressed or expressed at low levels in hematopoietic cells. We determined that the EGFR was expressed at a low level in the murine cytokine-dependent hematopoietic cell line FDC-P1 but not in an additional murine IL-3 dependent cell line FL5. EGF induced a mild effect on DNA synthesis and ERK activation in EGFR positive FDC-P1 cells but not EGFR negative FL5.12 cells. Addition of suboptimal concentrations of IL-3 synergized with EGF in stimulating DNA synthesis in EGFR-positive FDC-P1 cells. Likewise, the EGFR inhibitor AG1478 induced apoptosis in EGFR positive FDC-P1 cells but not EGFR negative FL5.12 cells. Both cell lines can be directly transformed to cytokine independence by activated EGFR (v-ERBB) expression in the absence of autocrine growth factors indicating that they are poised to fully utilize EGFR mediated signal transduction pathways as a means for proliferation. These results document the functional importance of endogenous EGFR signaling pathway in some hematopoietic cells.
Shelton
John G
JG
Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
Steelman
Linda S
LS
Abrams
Steven L
SL
White
Edmund R
ER
Akula
Shaw M
SM
Bertrand
Fred E
FE
Franklin
Richard A
RA
McCubrey
James A
JA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006413:Hematopoietic System / Q000187:drug effects*; D007377:Interleukin-3 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects; D015398:Signal Transduction
D007377:Interleukin-3; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases