Hypoxia inducible factor (HIF)-1α directly activates leptin receptor (Ob-R) in pancreatic cancer cells

He Ren, Lingling Jia, Tiansuo Zhao, Huan Zhang, Jing Chen, Shaoguang Yang, Jingcheng Liu, Ming Yu, Jihui Hao

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The aim of this study is to investigate the regulatory mechanism of leptin receptors (Ob-R) in pancreatic cancer. We found that the over-expression of hypoxia inducible factor (HIF-1)α and hypoxia up-regulated the expression of Ob-R in pancreatic cancer cells. When HIF-1α gene was silenced in vitro, the expression of Ob-R was significantly decreased. Xenograft mouse models showed that the inhibition of HIF-1α resulted in the concomitant decrease of Ob-R in vivo. In addition, HIF-1α expression was correlated with Ob-R in pancreatic cancer tissues by immunohistochemical staining. Clinical data showed that over-expression of HIF-1 was associated with pathological tumor node metastasis stage, lymph node metastasis and overall survival. HIF-1α directly bound to the hypoxia-responsive element (HRE) located in Ob-R gene promoter (-828/-832) and activated the transcription. Finally, we demonstrated that the silence of HIF-1α gene reversed the inhibitory effect of leptin/Ob-R in pancreatic cancer cells. Taken together, our results indicate that HIF-1α directly regulated Ob-R expression in pancreatic cancer, which might be a valuable therapeutic target for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)172-180
Number of pages9
JournalCancer Letters
Volume354
Issue number1
DOIs
StatePublished - Nov 1 2014

Fingerprint

Leptin Receptors
Hypoxia-Inducible Factor 1
Pancreatic Neoplasms
Neoplasm Metastasis
vpr Genes
Leptin
Heterografts
Genes
Lymph Nodes
Staining and Labeling

Keywords

  • Hypoxia inducible factor-1α (HIF-1α)
  • Leptin
  • Leptin receptor (Ob-R)
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hypoxia inducible factor (HIF)-1α directly activates leptin receptor (Ob-R) in pancreatic cancer cells. / Ren, He; Jia, Lingling; Zhao, Tiansuo; Zhang, Huan; Chen, Jing; Yang, Shaoguang; Liu, Jingcheng; Yu, Ming; Hao, Jihui.

In: Cancer Letters, Vol. 354, No. 1, 01.11.2014, p. 172-180.

Research output: Contribution to journalArticle

Ren, He ; Jia, Lingling ; Zhao, Tiansuo ; Zhang, Huan ; Chen, Jing ; Yang, Shaoguang ; Liu, Jingcheng ; Yu, Ming ; Hao, Jihui. / Hypoxia inducible factor (HIF)-1α directly activates leptin receptor (Ob-R) in pancreatic cancer cells. In: Cancer Letters. 2014 ; Vol. 354, No. 1. pp. 172-180.
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