Induction of Cdc25B expression by epidermal growth factor and transforming growth factor-alpha.
The dual specificity protein phosphatase Cdc25B regulates of the mitotic cell cycle checkpoint and is over expressed in human tumors. Given the importance of growth factors in initiating and sustaining cell proliferation, we examined their effects on Cdc25B protein expression in human cancer cells. Within 1h after epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) treatment, Cdc25B protein levels increased in growth factor responsive A549 and SCC25 cells, but not in non-responsive MDA-MB-231 cells. A functional consequence of elevated Cdc25B was implied by the concomitant decrease in phosphorylated cyclin dependent kinase, a known Cdc25B substrate, after growth factor treatment of A549 and SCC25 cells. The EGF-mediated induction of Cdc25B required a functional EGF receptor (ErbB1), as mouse embryonic fibroblasts lacking ErbB1 did not have increased Cdc25B levels after EGF treatment. Moreover, the EGFR receptor-selective tyrosine kinase inhibitor AG1478 and mitogen activated kinase kinase inhibitor U0126 blocked growth factor-mediated Cdc25B induction. Thus, EGF and TGF-alpha appear to induce cellular Cdc25B through the mitogen-activated protein kinase pathway.
Oguri
Tetsuya
T
Departments of Pharmacology and Chemistry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Nemoto
Kaoru
K
Bansal
Pallavi
P
Wipf
Peter
P
Lazo
John S
JS
D002070:Butadienes / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
D002070:Butadienes; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D009570:Nitriles; D016211:Transforming Growth Factor alpha; C113580:U 0126; D004815:Epidermal Growth Factor; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases