Antisense KGFR oligonucleotide inhibition of KGF-induced motility in breast cancer cells.
BACKGROUND
The metastasis of breast cancer is known to be directly associated with the motility of breast cancer cells. We have previously shown that keratinocyte growth factor (KGF) enhances the motility of estrogen receptor (ER)-positive breast cancer cells and that this motility response is associated with cellular levels of the KGF receptor (KGFR). Further, we observed that KGF treatment enhanced KGFR gene expression in MCF-7 cells. The objective of the present study was to examine the influence of antisense KGFR oligonucleotide treatment on the KGF-induced motility response in breast cancer cells.


METHODS
Both time-lapse video microscopy (TLVM) and culture wounding experiments were used to quantify cell motility. KGFR antisense effects on the expression of KGFR were determined by Western blotting, real time PCR and immunocytochemistry.


RESULTS
Antisense KGFR treatment significantly reduced both KGFR mRNA and protein expression. In addition, the antisense KGFR abolished the KGF-mediated cell motility response as early as 2 h following KGF treatment as observed by TLVM and lasting for up 48 h as observed by culture wounding. CONCLUSIOS: The results of this study indicate that KGFR activation and intracellular signaling mediates the KGF motility effect and suggests that KGFR may be an important new therapeutic target for the treatment or prevention of metastatic progression in breast cancer.
Departments of Pharmaceutical Sciences, Pathology and Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Xiao-Ping
XP
Zang
Megan R
MR
Lerner
S Terence
ST
Dunn
Daniel J
DJ
Brackett
J Thomas
JT
Pento
D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009362:Neoplasm Metastasis / Q000517:prevention & control; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D014407:Tumor Cells, Cultured
C496453:FGF7 protein, human; D016376:Oligonucleotides, Antisense; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor