Upregulation of VEGF-C by androgen depletion: The involvement of IGF-IR-FOXO pathway

Jinping Li, Enfeng Wang, Francesca Rinaldo, Kaustubh Datta

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Androgen ablation therapy is eventually followed by a more metastatic and androgen-refractory stage of prostate cancer. The detailed molecular mechanism of this gradual transition is not clearly understood. Recent reports correlate the high abundance of vascular endothelial growth factor-C (VEGF-C) to the lymph node metastasis seen in human prostate cancer (Tsurusaki et al., 1999). In this study, we report that androgen ablation in LNCaP cells augment the transcriptional upregulation of VEGF-C and the downregulation of the IGF-IR pathway, due to androgen withdrawal, is a potential mechanism for this observed VEGF-C transcription. Forkhead transcription factor FOXO-1, activated by SIRT-1, was identified as the downstream molecule within this pathway. Furthermore, the VEGF-C-induced increase of Bag-IL expression in LNCaP cells suggests that VEGF-C plays a role in the androgen-independent reactivation of the androgen receptor, resulting in androgen-refractorv prostate cancer growth.

Original languageEnglish (US)
Pages (from-to)5510-5520
Number of pages11
JournalOncogene
Volume24
Issue number35
DOIs
StatePublished - Aug 18 2005

Keywords

  • Androgen
  • IGF-IR
  • Metastasis
  • Prostate cancer
  • VEGF-C

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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