Estrogen receptor activation at serine 305 is sufficient to upregulate cyclin D1 in breast cancer cells.

摘要: Recent studies have shown that p21-activated kinase 1 (Pak1) phosphorylates estrogen receptor-α (ERα) at Ser 305 and also promotes its transactivation function. Here, we sought to investigate whether substitution of serine in ER with glutamic acid (ERα-S305E), which mimics the phosphorylation state, would influence status ER-target genes. To explore this possibility, generated clones overexpressing ERα-S305E ER-negative MDA-MB-231 cells analyzed ER-regulated genes using a gene array. Results indicated expression is sufficient upregulate few but not all genes, i.e., cyclin D1 zinc finger protein 147 (estrogen-responsive protein), while there was no significant change remaining on In addition, found an increased as well nuclear accumulation expressing compared level WT-ERα or pcDNA. Furthermore, ERα-S305E, mutation ERα-S305 alanine, enhanced promoter activity. These findings suggest ERα activation S305 D1, implicated progression breast cancer. Phosphorylation by Pak1 upstream regulators could subset ligand-independent manner hence, might contribute toward development hormone independence cancer cells.