Molecules and Cells

, Volume 32, Issue 1, pp 107–111 | Cite as

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 KangEmail author


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.


E2F1 p38 kinase PI3-kinase Pin1 tamoxifen-resistant breast cancer VEGF 


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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
    Email author
  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

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