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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS
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Published on: December 21, 2011

VDUP1 potentiates Ras-mediated angiogenesis via ROS production in endothelial cells.

Z H Piao1, S R Yoon, M S Kim

  • 1Korea Research Institute of Bioscience and Biotechnology, Stem Cell Research Center, Daejon, Republic of Korea.

Cellular and Molecular Biology (Noisy-Le-Grand, France)
|March 10, 2009
PubMed
Summary
This summary is machine-generated.

Vitamin D3 up-regulated protein 1 (VDUP1) acts as a tumor suppressor by increasing reactive oxygen species (ROS) and promoting angiogenesis. Its role in Ras-mediated endothelial cell proliferation and tumor growth is significant.

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Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Vitamin D3 up-regulated protein 1 (VDUP1) is a known tumor suppressor.
  • VDUP1 expression is frequently reduced in various cancer cells.
  • VDUP1 inhibits thioredoxin activity, leading to increased cellular reactive oxygen species (ROS).

Purpose of the Study:

  • To investigate the role of VDUP1 in angiogenesis and endothelial cell proliferation.
  • To understand the mechanism by which VDUP1 influences Ras-mediated processes.

Main Methods:

  • Overexpression of VDUP1 and the oncogene Ras in endothelial cells.
  • Measurement of ROS production.
  • Assessment of cell proliferation, resistance to anchorage-dependent cell death, and tube formation.
  • Use of ROS scavengers to evaluate the role of ROS.

Main Results:

  • Ras overexpression upregulates VDUP1 expression.
  • Enforced VDUP1 expression in Ras-overexpressing endothelial cells increases ROS production and proliferation.
  • VDUP1 overexpression enhances resistance to cell death and promotes tube formation in these cells.
  • ROS scavenging attenuates the effect of VDUP1 on tube formation.

Conclusions:

  • VDUP1 plays a role in Ras-mediated angiogenesis through ROS generation in endothelial cells.
  • VDUP1 may be a therapeutic target for cancers driven by Ras signaling.