Role of the BLT2, a leukotriene B4 receptor, in Ras transformation

Min Hyuk Yoo, Haiwon Song, Chang Hoon Woo, Heung Gyu Kim, Jae Hong Kim

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46 Citations (Scopus)


Oncogenic Ras is known to drive both the Rac and Raf-MAP-kinase pathways, which act in concert to cause cell transformation. Unlike the Raf-MAP-kinase cascade, however, the downstream elements of Rac pathway are not fully understood. Previously, we showed that cytosolic phospholipase A2 (cPLA2) and subsequent metabolism of arachidonic acid act downstream of Rac to mediate the transformation signaling induced by Ha-RasV12. In the present study, we observed that leukotriene B4 (LTB 4) and its synthetic enzymes as well as BLT2, the low-affinity LTB4 receptor, are all elevated in Ha-RasV12-transformed cells. In addition, the malignant phenotypes of Ras-transformed cells were markedly inhibited by BLT2 blockade, as was their tumorigenicity in vivo. Finally, in situ hybridization analysis revealed that expression of BLT2 is significantly upregulated in a variety of human cancers. Taken together, our results suggest that an LTB4-BLT2-linked cascade plays a crucial mediatory role in the cell transformation induced by oncogenic Ha-Ras V12, possibly acting downstream of Rac-cPLA2.

Original languageEnglish
Pages (from-to)9259-9268
Number of pages10
Issue number57
Publication statusPublished - 2004 Dec 9

Bibliographical note

Funding Information:
We would like to thank Dr Takao Shimizu and Dr Takehiko Yokomizo (The University of Tokyo, Tokyo, Japan) for kindly providing BLT expression plasmids and Pfizer Inc. for generously providing the leukotriene B4 receptor inhibitor CP105696. This work was supported by grants from the SRC program (Aging and Apoptosis Research Center) (2002) from the Korea Science and Engineering Foundation (KOSEF), a Molecular and Cellular BioDiscovery Research Program grant (M10311000003-03B4500-00100), and a Frontier 21 Programs (Proteomics; to JH Kim) from the Ministry of Science and Technology, South Korea.


  • BLT2
  • Cancer
  • Leukotriene B
  • Ras transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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