TY - JOUR
T1 - EGF induces cell motility and multi-drug resistance gene expression in breast cancer cells
AU - Garcia, Ruben
AU - Franklin, Richard A.
AU - McCubrey, James A.
N1 - Funding Information:
RG, RAF and JAM were supported in part by R01CA098195 from the National Cancer Institute (USA). We thank Mr. William Chappell for help with the transient assay. We thank Ms. Linda Steelman for the growth of bacterial plasmids and cell lines. We thank Dr. William Beck at the University of Illinois, Chicago for generously providing the MDR1 promoter luciferase construct.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - The epidermal growth factor receptor (EGFR) is important for normal development, differentiation, and cell proliferation. Deregulation of EGFR has been observed in breast cancer. EGFR and signal pathways activated by these receptors have been associated with an advanced tumor stage and a poor clinical prognosis in breast cancer; however, the precise mechanisms responsible for this process are still not known. Here we show that treatment of MCF-7 breast cancer cells with EGF activated Akt and ERK, induced morphological changes, and increased cell motility. In addition, the constitutive expression of Raf-1 and the use of a MEK inhibitor demonstrated the participation of the Raf/MEK/ERK pathway in these processes. Importantly we detected that EGF induced MRP-1, 3, 5 and 7 gene expression and an increase in MRP1 promoter activity. In conclusion, treatment of MCF-7 breast cancer cells with EGF, in the absence of other growth factors, resulted in activation of EGFR signal transduction pathways; which were related with cell motility and drug resistance.
AB - The epidermal growth factor receptor (EGFR) is important for normal development, differentiation, and cell proliferation. Deregulation of EGFR has been observed in breast cancer. EGFR and signal pathways activated by these receptors have been associated with an advanced tumor stage and a poor clinical prognosis in breast cancer; however, the precise mechanisms responsible for this process are still not known. Here we show that treatment of MCF-7 breast cancer cells with EGF activated Akt and ERK, induced morphological changes, and increased cell motility. In addition, the constitutive expression of Raf-1 and the use of a MEK inhibitor demonstrated the participation of the Raf/MEK/ERK pathway in these processes. Importantly we detected that EGF induced MRP-1, 3, 5 and 7 gene expression and an increase in MRP1 promoter activity. In conclusion, treatment of MCF-7 breast cancer cells with EGF, in the absence of other growth factors, resulted in activation of EGFR signal transduction pathways; which were related with cell motility and drug resistance.
KW - Breast cancer
KW - Drug resistance
KW - EGF
KW - EGFR
KW - Motility
UR - http://www.scopus.com/inward/record.url?scp=33845455068&partnerID=8YFLogxK
U2 - 10.4161/cc.5.23.3535
DO - 10.4161/cc.5.23.3535
M3 - Artículo
SN - 1538-4101
VL - 5
SP - 2820
EP - 2826
JO - Cell Cycle
JF - Cell Cycle
IS - 23
ER -