Although production of reactive oxygen species (ROS) by oncogenic Ras is thought to be crucial for Ras transformation, very little is known about the signaling mechanism involved. In the present study, we investigated whether BLT2, a low-affinity leukotriene B4 receptor, is involved in the generation of ROS in H-RasV12-transformed fibroblasts. We show that downregulation of BLT2 using RNA interference or antisense oligonucleotides inhibits ROS generation, and that Nox1 acts downstream of BLT2. Moreover, BLT2 overexpression caused increased ROS production and partial transformation. Taken together, our results suggest that a BLT2-Nox1-linked cascade is responsible for the elevated ROS generation in Ras-transformed cells. Our finding may contribute to clarifying the signaling events underlying the enhanced levels of ROS frequently observed in various transformed cells and possibly serve as a basis for developing new therapeutic strategies for human cancers.
|Number of pages
|Free Radical Biology and Medicine
|Published - 2008 Feb 15
Bibliographical noteFunding Information:
This work was supported by grants from the Frontier 21 Program (Proteomics), the Molecular and Cellular BioDiscovery Research Program, the Diseases Network Research Program, and the SRC program (Aging and Apoptosis Research Center) from the Korea Ministry of Science and Technology. We thank Dr. Takao Shimizu and Dr. Takehiko Yokomizo (University of Tokyo, Tokyo, Japan) for the BLT2 expression plasmids.
- Leukotriene B
- Ras transformation
ASJC Scopus subject areas
- Physiology (medical)