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

Journal Article (Journal Article)

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-refractory prostate cancer growth.

Full Text

Duke Authors

Cited Authors

  • Li, J; Wang, E; Rinaldo, F; Datta, K

Published Date

  • August 18, 2005

Published In

Volume / Issue

  • 24 / 35

Start / End Page

  • 5510 - 5520

PubMed ID

  • 15897888

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1208693


  • eng

Conference Location

  • England