Role of the BLT2, a leukotriene B4 receptor, in Ras transformation.
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-Ras(V12). In the present study, we observed that leukotriene B4 (LTB4) and its synthetic enzymes as well as BLT2, the low-affinity LTB4 receptor, are all elevated in Ha-Ras(V12)-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.[1]References
- Role of the BLT2, a leukotriene B4 receptor, in Ras transformation. Yoo, M.H., Song, H., Woo, C.H., Kim, H., Kim, J.H. Oncogene (2004) [Pubmed]
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