ScholarWorks@숙명여자대학교

초록

Cancerous inhibitor of PP2A (CIP2A) stimulates the proliferation of various cancer cells, and 17 beta-estradiol (E-2) enhances the proliferation of breast cancer cells. E-2 activates epidermal growth factor receptor (EGFR), stimulating the MEK1/2 and PI3K pathways, and CIP2A expression is increased by the MEK1/2-induced transcription factor ETS1. It is possible for E-2 to increase CIP2A expression. This study examined whether E-2 could increase CIP2A expression and whether CIP2A is highly expressed in estrogen receptor (ER)-positive breast cancer tissues. E-2 increased CIP2A expression at the translational level in a c-MYC-independent manner in MCF-7 cells. E-2-enhanced proliferation was impaired without CIP2A expression. E-2-stimulated EGFR activated the MAPK and PI3K pathways, which converged to activate p70 S6 kinase (S6K). Phosphorylation at all the three phosphorylation sites (S424/T421, T229, and T389) on S6K was required for the phosphorylation of eukaryotic initiation factor 4B (eIF4B), which was responsible for the increase in CIP2A translation. Furthermore, CIP2A expression was higher in ER-positive tissues than in ER-negative tissues. This is the first study, to our knowledge, to demonstrate that CIP2A is a key factor in E-2-enhanced proliferation and that estrogen regulates CIP2A expression by non-genomic action through EGFR. Endocrine-Related Cancer

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