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. MATERIALS AND 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.
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 KGFRoligonucleotide treatment on the KGF-induced motility response in breast cancer cells. MATERIALS AND 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.