Molecules and Cells

, Volume 32, Issue 1, pp 107–111

PI3-Kinase/p38 kinase-dependent E2F1 activation is critical for pin1 induction in tamoxifen-resistant breast cancer cells

  • Kwang Youl Lee
  • Jeong Woon Lee
  • Hyun Jeong Nam
  • Jeong-Hyun Shim
  • Youngsup Song
  • Keon Wook Kang
Article

DOI: 10.1007/s10059-011-0074-y

Cite this article as:
Lee, K.Y., Lee, J.W., Nam, H.J. et al. Mol Cells (2011) 32: 107. doi:10.1007/s10059-011-0074-y

Abstract

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. We have shown that Pin1, a peptidyl prolyl isomerase, is consistently overexpressed in TAM-resistant MCF-7 cells (TAMR-MCF-7 cells) and plays a key role in the enhanced angiogenic potential of TAMR-MCF-7 cells. In the present study, we focused on signaling pathways for Pin1 up-regulation in TAMR-MCF-7 cells. Relative to MCF-7 cells, Pin1 gene transcription and E2 transcription factor1 (E2F1) expression were enhanced in TAMR-MCF-7 cells. E2F1 siRNA significantly reduced both the protein expression and the promoter transcriptional activity of Pin1. Activities of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK) and p38 kinase were all higher in TAMR-MCF-7 cells than in control MCF-7 cells and the enhanced Pin1 and E2F1 expression in TAMR-MCF-7 cells was reversed by inhibition of PI3K or p38 kinase. Moreover, the higher production of vascular endothelial growth factor (VEGF) in TAMR-MCF-7 cells was significantly diminished by suppression of PI3K or p38 kinase. These results suggest that Pin1 overexpression and subsequent VEGF production in TAMR-MCF-7 cells are mediated through PI3-kinase or p38 kinase-dependent E2F1 activation.

Keywords

E2F1p38 kinasePI3-kinasePin1tamoxifen-resistant breast cancerVEGF

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2011

Authors and Affiliations

  • Kwang Youl Lee
    • 2
  • Jeong Woon Lee
    • 1
  • Hyun Jeong Nam
    • 1
  • Jeong-Hyun Shim
    • 3
  • Youngsup Song
    • 4
  • Keon Wook Kang
    • 1
  1. 1.Brain Korea 21 Project Team, College of PharmacyChosun UniversityGwangjuKorea
  2. 2.College of PharmacyChonnam National UniversityGwangjuKorea
  3. 3.School of MedicineSoonchunhyang UniversityAsanKorea
  4. 4.The Salk Institute for Biological StudiesLa JollaUSA