Abstract
Epidermal growth factor receptor (EGFR) signaling is one of the complex signal transduction pathways. Following EGF stimulation, tensin3 expression is downregulated and CTEN is upregulated, to a level that is sufficient for displacement of tensin3 from integrin. Then tensin3 dissociates from focal adhesion, leading to the breakdown of F-actin and initiation of cell migration in breast cancer. However, the mechanism of EGFR-induced CTEN gene expression is still unclear. Our results have shown that knockdown p300 expression could decrease EGF-induced CTEN mRNA and protein levels in a normal human prostate cell lines, RWPE-1, and a human cervical cancer cell line, HeLa. It indicates that p300 participates in the EGF-regulated CTEN expression. We further demonstrate that after EGF stimulation, p300 is recruited to CTEN promoter through MEK/ERK pathway in HeLa cells, and increases histone acetylation on CTEN promoter to activate CTEN gene expression. EGF also induces the phosphorylation of p300 through MEK/ERK pathway in HeLa cells. Therefore, our study suggests that EGF signaling induces the phosphorylation of p300 through MEK/ERK pathway, thereby enhancing its histone acetyltransferase activity, and in turn recruits an increased level of p300 to CTEN promoter to activate CTEN gene expression.
Published Version
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