Abstract
Background:
Keratinocyte growth factor (KGF) has been shown to induce breast cancer metastasis in animal models. cDNA microarrays have revealed that KGF increased Wilms tumor 1 (WT1) and focal adhesion kinase (FAK) expression in breast cancer cells. The role of WT1 and FAK in KGF signaling was investigated.
Materials and methods:
A cell culture wounding model was used to study the effects of WT1 and FAK down-regulation on KGF-induced proliferation and motility in breast cancer cells.
Results:
WT1 down-regulation inhibited KGF-mediated proliferation and motility of breast cancer cells, while FAK down-regulation inhibited proliferation, but had no significant effect on cell motility. WT1 down-regulation, but not FAK down-regulation, led to Erk1,2 inactivation.
Conclusion:
KGF-mediated signaling employs WT1 and FAK to regulate breast cancer cell proliferation and motility and may represent therapeutic targets for the prevention of breast cancer progression.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Breast Neoplasms / enzymology
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Cycle Proteins
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Cell Line, Tumor
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Cell Movement / physiology
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Down-Regulation
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Enzyme Activation
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Fibroblast Growth Factor 7 / antagonists & inhibitors
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Fibroblast Growth Factor 7 / metabolism*
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Fibroblast Growth Factor 7 / pharmacology
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Focal Adhesion Protein-Tyrosine Kinases / biosynthesis
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Focal Adhesion Protein-Tyrosine Kinases / metabolism*
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GRB2 Adaptor Protein / biosynthesis
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Humans
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / metabolism*
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Phosphorylation
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RNA Splicing Factors
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Recombinant Proteins / pharmacology
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Signal Transduction
Substances
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Cell Cycle Proteins
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GRB2 Adaptor Protein
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GRB2 protein, human
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Nuclear Proteins
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RNA Splicing Factors
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Recombinant Proteins
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WTAP protein, human
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Fibroblast Growth Factor 7
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Focal Adhesion Protein-Tyrosine Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3