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

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Yoo MH,Song H,Woo CH,Kim H,Kim JH

doi

10.1038/sj.onc.1208151

subject

Has Abstract

pub_date

2004-12-09 00:00:00

pages

9259-68

issue

57

eissn

0950-9232

issn

1476-5594

pii

1208151

journal_volume

23

pub_type

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