Cell death of MCF-7 human breast cancer cells induced by EGFR activation in the absence of other growth factors.
The epidermal growth factor (EGF) receptor (EGFR) plays an important role in the growth and progression of breast cancer. Overexpression of EGFR or the high activity of EGFR signal pathway has been related with increases in cell proliferation and a poor prognosis in patients with breast cancer. Several human breast cancer cell lines depend on estrogen for their proliferation. EGF may bypass the requirement of estrogen for the proliferation of breast cancer cells. To evaluate this hypothesis, MCF-7 breast cancer cells were stimulated with EGF and the effects on cell proliferation, signal pathways, and cell cycle progression were determined. The results demonstrate that EGF stimulation in the absence of others growth factors induced a modest effect on cell proliferation and the induction of a cellular arrest in the G(1) phase of the cell cycle. Although phosphorylation of AKT and ERK proteins were detected, this phosphorylation was insufficient to support of cell cycle progression. Cellular arrest in G(1) phase was accompanied by an increase in p21(CIP1) protein, down regulation of the BCL-2 protein, induction of caspase-8, and ARHI/NOEY2 an imprinted tumor suppressor gene. These results indicate that EGFR activation by itself is not sufficient for the proliferation of breast cancer cells and suggest the existence of a mechanism that induces apoptosis upon EGFR activation.
Garcia
Ruben
R
Department of Microbiology & Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA.
Franklin
Richard A
RA
McCubrey
James A
JA
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000819:agonists* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; C117386:DIRAS3 protein, human; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases; D020741:rho GTP-Binding Proteins