Loss of NKX3.1 favors vascular endothelial growth factor-C expression in prostate cancer

Heyu Zhang, Michael H. Muders, Jinping Li, Francesca Rinaldo, Donald J. Tindall, Kaustubh Datta

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Decreased levels of the prostate-specific homeobox protein NKX3.1 are correlated with hormone-refractory and metastatic prostate cancer. Thus, it is compellingto define the NKX3.1-regulated genes that may be important for the progression of the advanced stage of the disease. In this study, we showed that vascular endothelial growth factor-C (VEGF-C) is one such target gene of NKX3.1. NKX3.1 inhibited VEGF-C expression in prostate cancer, and the loss of NKX3.1 led to increased VEGF-C expression. Histone deacetylase 1 acted as a corepressor of VEGF-C expression along with NKX3.1. Activated RalA acted in synergy with the loss of NKX3.1 for VEGF-C transcription. Patients with deletions at chromosome 8p21.1-p21.2 as a sole deletion developed lymph node metastasis. Interestingly, the higher expression of VEGF-C in prostate cancer is also correlated with lymph node metastasis. Therefore, regulation of VEGF-C expression by NKX3.1 provides a possible mechanism by which the loss of NKX3.1 protein level leads to lymphangiogenesis in the late stages of advanced prostate cancer.

Original languageEnglish (US)
Pages (from-to)8770-8778
Number of pages9
JournalCancer Research
Volume68
Issue number21
DOIs
StatePublished - Nov 1 2008

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Vascular Endothelial Growth Factor C
Prostatic Neoplasms
Lymph Nodes
Histone Deacetylase 1
Lymphangiogenesis
Neoplasm Metastasis
Homeodomain Proteins
Co-Repressor Proteins
Chromosome Deletion
Genes
Prostate
Hormones

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Loss of NKX3.1 favors vascular endothelial growth factor-C expression in prostate cancer. / Zhang, Heyu; Muders, Michael H.; Li, Jinping; Rinaldo, Francesca; Tindall, Donald J.; Datta, Kaustubh.

In: Cancer Research, Vol. 68, No. 21, 01.11.2008, p. 8770-8778.

Research output: Contribution to journalArticle

Zhang, Heyu ; Muders, Michael H. ; Li, Jinping ; Rinaldo, Francesca ; Tindall, Donald J. ; Datta, Kaustubh. / Loss of NKX3.1 favors vascular endothelial growth factor-C expression in prostate cancer. In: Cancer Research. 2008 ; Vol. 68, No. 21. pp. 8770-8778.
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