Journal
CANCER BIOLOGY & THERAPY
Volume 11, Issue 5, Pages 497-511Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.11.5.14667
Keywords
ER beta; PEA3; IL-8; breast cancer; invasion; HER2; promoter
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Funding
- National Basic Research Program of China [2006CB910501]
- National Natural Science Foundation of China [30371580, 30572109, 81072166]
- Shanghai Science and Technology Committee [03J14019, 06DJ14004, 06DZ19504]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
- Shanghai Pujiang Program
- Shanghai Municipal Education Commission [09ZZ04]
- Natural Science Foundation of Shanghai [09ZR1406900]
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Metastasis represents the major remaining cause of mortality in human breast cancer. Interleukin-8 (IL-8), a proinflammatory chemokine, plays an important role during tumor angiogenesis and metastasis. In this study, we found that IL-8 and ERbeta (ER beta) showed positive association. Overexpression of ER beta or PEA 3 could upregulate IL-8 promoter activity, mRNA and secretion; silencing of ER beta or PEA 3 decreased IL-8 mRNA and secretion. ER beta and PEA 3 increased IL-8 expression through binding to the IL-8 promoter and increased cell invasion. HER2 could increase ER beta and PEA 3 expression and their binding to the IL-8 promoter. We conclude that ER beta and PEA 3 play important roles in tumor invasion by regulating IL-8 expression, and HER2 maybe the upstream of ER beta and PEA3-IL-8 pathway.
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