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 journalArticle

49 Citations (Scopus)

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

Fingerprint

Vascular Endothelial Growth Factor C
Androgens
Up-Regulation
Prostatic Neoplasms
Forkhead Transcription Factors
Androgen Receptors
Down-Regulation
Lymph Nodes
Neoplasm Metastasis
Growth

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Upregulation of VEGF-C by androgen depletion : The involvement of IGF-IR-FOXO pathway. / Li, Jinping; Wang, Enfeng; Rinaldo, Francesca; Datta, Kaustubh.

In: Oncogene, Vol. 24, No. 35, 18.08.2005, p. 5510-5520.

Research output: Contribution to journalArticle

Li, Jinping ; Wang, Enfeng ; Rinaldo, Francesca ; Datta, Kaustubh. / Upregulation of VEGF-C by androgen depletion : The involvement of IGF-IR-FOXO pathway. In: Oncogene. 2005 ; Vol. 24, No. 35. pp. 5510-5520.
@article{70238b34f8ca40d8b5872ca8835a05ae,
title = "Upregulation of VEGF-C by androgen depletion: The involvement of IGF-IR-FOXO pathway",
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.",
keywords = "Androgen, IGF-IR, Metastasis, Prostate cancer, VEGF-C",
author = "Jinping Li and Enfeng Wang and Francesca Rinaldo and Kaustubh Datta",
year = "2005",
month = "8",
day = "18",
doi = "10.1038/sj.onc.1208693",
language = "English (US)",
volume = "24",
pages = "5510--5520",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "35",

}

TY - JOUR

T1 - Upregulation of VEGF-C by androgen depletion

T2 - The involvement of IGF-IR-FOXO pathway

AU - Li, Jinping

AU - Wang, Enfeng

AU - Rinaldo, Francesca

AU - Datta, Kaustubh

PY - 2005/8/18

Y1 - 2005/8/18

N2 - 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.

AB - 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.

KW - Androgen

KW - IGF-IR

KW - Metastasis

KW - Prostate cancer

KW - VEGF-C

UR - http://www.scopus.com/inward/record.url?scp=24644501741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24644501741&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1208693

DO - 10.1038/sj.onc.1208693

M3 - Article

C2 - 15897888

AN - SCOPUS:24644501741

VL - 24

SP - 5510

EP - 5520

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 35

ER -