Wilms' tumor 1 protein and focal adhesion kinase mediate keratinocyte growth factor signaling in breast cancer cells.
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.


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.


CONCLUSIONS
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.
Zang
Xiao-Ping
XP
Department of Pharmaceutical Sciences, University of Oklahoma, Health Sciences Center, Oklahoma City, OK, USA.
Pento
J Thomas
JT
Tari
Ana M
AM
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D004789:Enzyme Activation; D051523:Fibroblast Growth Factor 7 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000096:biosynthesis; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D000072260:RNA Splicing Factors; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D011994:Recombinant Proteins; C419554:WTAP protein, human; D051523:Fibroblast Growth Factor 7; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3