Abstract
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 ERβ showed positive association. Overexpression of ERβ or PEA3 could up-regulate IL-8 promoter activity, mRNA and secretion; silencing of ERβ or PEA3 decreased IL-8 mRNA and secretion. ERβ and PEA3 increased IL-8 expression through binding to the IL-8 promoter and increased cell invasion. HER2 could increase ERβ and PEA3 expression and their binding to the IL-8 promoter. We conclude that ERβ and PEA3 play important roles in tumor invasion by regulating IL-8 expression, and HER2 maybe the upstream of ERβ and PEA3 - IL-8 pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology*
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Cell Line, Tumor
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Estrogen Receptor beta / genetics
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Estrogen Receptor beta / metabolism*
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Female
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Humans
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Interleukin-8 / genetics
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Interleukin-8 / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Neovascularization, Pathologic
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Promoter Regions, Genetic
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / metabolism*
Substances
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Estrogen Receptor beta
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Interleukin-8
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RNA, Messenger
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Transcription Factors
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transcription factor PEA3
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ERBB2 protein, human
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Receptor, ErbB-2