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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
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Estradiol enhances CIP2A expression by the activation of p70 S6 kinase

Yeon A Choi1, Ja Seung Koo, Jeong Su Park

  • 1Department of Life Science, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.

Endocrine-Related Cancer
|November 28, 2013
PubMed

Insights

Estrogen (E₂) enhances breast cancer cell proliferation by increasing cancerous inhibitor of PP2A (CIP2A) expression via the epidermal growth factor receptor (EGFR) pathway. CIP2A is crucial for this E₂-driven growth and is elevated in ER-positive breast cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Endocrinology

Background:

  • Cancerous inhibitor of PP2A (CIP2A) promotes cancer cell proliferation.
  • 17β-estradiol (E₂) enhances breast cancer cell proliferation.
  • E₂ signaling involves epidermal growth factor receptor (EGFR) and downstream pathways like MEK1/2 and PI3K.

Purpose of the Study:

  • To investigate if E₂ increases CIP2A expression.
  • To determine if CIP2A is highly expressed in estrogen receptor (ER)-positive breast cancer.
  • To elucidate the mechanism by which E₂ regulates CIP2A.

Main Methods:

  • Utilized MCF-7 breast cancer cells.
  • Analyzed CIP2A expression at the translational level.
  • Investigated the roles of EGFR, MAPK, PI3K, p70 S6 kinase (S6K), and eukaryotic initiation factor 4B (eIF4B).
  • Compared CIP2A expression in ER-positive versus ER-negative human breast cancer tissues.

Main Results:

  • E₂ increased CIP2A expression translationally, independent of c-MYC.
  • E₂-enhanced proliferation was dependent on CIP2A.
  • E₂-stimulated EGFR activated MAPK and PI3K pathways, leading to S6K activation.
  • S6K phosphorylation was essential for eIF4B phosphorylation, which increased CIP2A translation.
  • CIP2A expression was significantly higher in ER-positive tissues compared to ER-negative tissues.

Conclusions:

  • CIP2A is a key mediator of E₂-enhanced breast cancer cell proliferation.
  • Estrogen regulates CIP2A expression through non-genomic action via the EGFR pathway.
  • Elevated CIP2A expression in ER-positive breast cancer suggests its clinical relevance.
Keywords:
CIP2AER-positive human breast cancer cellsMAPK pathwayPI3K/AKTbreast cancerestradiol (E2)p70 S6K

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