Epidermal growth factor receptor-regulated human bladder cancer motility is in part a phosphatidylinositol 3-kinase-mediated process.
Although overexpression of the epidermal growth factor receptor (EGFR) has been strongly associated with the transition from superficial to invasive human bladder cancer, the exact molecular pathways by which this gene effectively triggers or facilitates the invasive process are not completely understood. Because enhanced cellular motility is a prerequisite for invasion, we chose to determine how EGFR signaling impacts cellular motility of human bladder cancer in vitro in a cell model of human bladder cancer that closely mimics the human disease. Using a stable antisense approach to diminish EGFR expression, we obtained data that support the role of EGFR in mediating bladder cancer motility. These results also demonstrate that EGFR plays an important role in bladder cancer motility, even in the presence of a mutated and overexpressing Ras protein, and suggest the possibility that Ras-independent EGFR motility signaling is a significant pathway used by bladder cancer cells. In support of this concept, using specific pharmacological inhibition of phosphatidylinositol 3-kinase, we show that this mediator is involved in EGFR motility signaling in this system. Knowledge of the pathways used by EGFR to induce motility and subsequent invasion may lead to development of methods to prevent or retard the progression of aggressive superficial bladder tumors.
Theodorescu
D
D
Department of Urology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Laderoute
K R
KR
Gulding
K M
KM
D002455:Cell Division; D002465:Cell Movement; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis*; D006801:Humans; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors