Pro-survival of estrogen receptor-negative breast cancer cells is regulated by a BLT2-reactive oxygen species-linked signaling pathway
- Authors
- Choi, Jung-A; Lee, Jin-Wook; Kim, Hyunju; Kim, Eun-Young; Seo, Ji-Min; Ko, Jesang; Kim, Jae-Hong
- Issue Date
- 4월-2010
- Publisher
- OXFORD UNIV PRESS
- Citation
- CARCINOGENESIS, v.31, no.4, pp.543 - 551
- Indexed
- SCIE
SCOPUS
- Journal Title
- CARCINOGENESIS
- Volume
- 31
- Number
- 4
- Start Page
- 543
- End Page
- 551
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/116681
- DOI
- 10.1093/carcin/bgp203
- ISSN
- 0143-3334
- Abstract
- Leukotriene B-4 (LTB4) is an inflammatory mediator with potent biological activities in the pathogenesis of many inflammatory diseases. In the present study, we found that expression of BLT2, a low-affinity LTB4 receptor, is significantly upregulated in breast cancer cells. In addition, we observed that inhibition of BLT2 by a specific antagonist, LY255283, or by siBLT2 RNA interference caused dramatic apoptotic cell death in breast cancer cells, especially in the estrogen receptor (ER)-negative MDA-MB-468 and MDA-MB-453 cells, suggesting a role for BLT2 in survival of these breast cancer cells. In an approach to understand the downstream mechanism by which BLT2 mediates the potential pro-survival signaling, we found that the elevated reactive oxygen species (ROS) generation is associated with BLT2-mediated survival. Expression of Nox1, a member of the NADPH oxidase family, is also highly upregulated in a BLT2-dependent manner in these breast cancer cells, suggesting that 'Nox1-derived ROS' lie downstream of BLT2. Consistent with the proposed role of 'Nox1-ROS' in pro-survival signaling, knockdown of Nox1 with siNox1 or treatment with a ROS scavenging agent caused dramatic apoptotic death in these breast cancer cells. Taken together, our results demonstrate, for the first time, that the 'BLT2-Nox1-ROS'-linked cascade is involved in the pro-survival signaling, especially in ER-negative breast cancer cells.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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