Mechanism of PBK/TOPK in Mediating MEK-Independent ERK Activation in Breast Cancer Cells
LI Xiaoyong1, LIU Tao1, LI Jian1, LIU Chao1, LIU Yuhong2*
The aim of this article was to investigate the EGF (epidermal growth factor)-mediated MEKindependent ERK activation pathway in breast cancer cells. Under the stimulation of EGF detected by Western blot, siRNA inhibited the p-ERK level of T47D cells after MEK1/2 treatment. This article was to confirm the presence of EGF-mediated MEK-independent ERK activation in T47D cells. The phosphorylation level of ERK mediated by EGF in T47D cells was then measured after inhibition of the activity of related kinases (AC, PKC, SRC, PI3K, PDK1 and Akt) by small molecular inhibitors of kinases that may be involved in MEK independentERK activation. After MEK1/2 inhibiton, T47D cells retained partial p-ERK under the stimulation of EGF, EGF-mediated MEKindependent ERK phosphorylation pathway in T47D cells. The AC, and PKC and Src inhibiton by small molecule inhibitors have little effect on MEK-independent ERK activation pathway. The phosphorylation level of ERK was significantly decreased after inhibition of PI3K, PDK1 and Akt by small molecule inhibitors, suggesting that the kinase downstream of the PI3K/Akt pathway was involved in the EGF-mediated MEK-independent ERK activation pathway in T47D cells. After PBK/TOPK downstream of PI3K/Akt pathway interfered by siRNA and MEK1/2 function inhibited treated by U0126, p-ERK was almost undetectable, suggesting that PBK/TOPK was involved in EGF-mediated MEK-independent ERK activation pathway in T47D cells. EGF-mediated MEK-independent ERK activation pathway is present in breast cancer anti-estrogen drug-resistant strain T47D cells, and this pathway is regulated by PBK/TOPK downstream of PI3K/Akt.
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