Estradiol enhances CIP2A expression by the activation of p70 S6 kinase

Yeon A. Choi, Ja Seung Koo, Jeong Su Park, Mi Young Park, Ae Lee Jeong, Ki Sook Oh, Young Yang

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Cancerous inhibitor of PP2A (CIP2A) stimulates the proliferation of various cancer cells, and 17b-estradiol (E2) enhances the proliferation of breast cancer cells. E2 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 E2 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. E2-enhanced proliferation was impaired without CIP2A expression. E2-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 E2-enhanced proliferation and that estrogen regulates CIP2A expression by non-genomic action through EGFR.

Original languageEnglish
Pages (from-to)189-202
Number of pages14
JournalEndocrine-Related Cancer
Volume21
Issue number2
DOIs
Publication statusPublished - 2014 Apr

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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