The role of Cdc25B in lung cancer progression

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Given the importance of growth factors in initiating and sustaining cell proliferation, we examined their effects on Cdc25B protein expression inhuman cancer cells. Within 1h after epidermal growth factor(EGF) or transforming growth factor-α(TGF-α) treatment, Cdc25B protein levels increased in lung cancer cell line A549 cells. A functional consequence of elevated Cdc25B was implied by the concomitant decrease in phosphorylated cyclin dependent kinase. 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-αappear to induce cellular Cdc25B through the mitogen-activated protein kinase pathway. Further, Cdc25B is a co-activator for the estrogen receptor(ER). Because of potential cross talk between the ER and growth factor signaling pathways, we examined the effects of heregulin (HEG)-β1 on Cdc25B expression and Cdc25B-ERα interactions. HEG-β1 induced Cdc25B protein levels in Her2/neu-expressing A549 cells and this Cdc25B induction by HEG-β1 was blocked by the HER2/neu tyrosine kinase inhibitor AG879 and the MEK inhibitor U0126. HEG-β1 caused a concentration-and time-dependent increase in Cdc25B-ERα interactions in breast cancer cell line MCF-7 cells grown in estrogenic substance-free medium. The increased Cdc25B-ERα interaction after HEG-β1 was also blocked by AG879 and U0126. Thus, HEG-β1 induction of Cdc25B expression and ERα co-activation under hormone deprivation require a competent mitogen-activated protein kinase pathway.