ERβ and PEA3 co-activate IL-8 expression and promote the invasion of breast cancer cells.
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.
Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, China.
Ying
Y
Chen
Li
L
Chen
Ji-Yu
JY
Li
Naofumi
N
Mukaida
Qiaoqiao
Q
Wang
Chen
C
Yang
Wen-Jin
WJ
Yin
Xiao-Hua
XH
Zeng
Wei
W
Jin
Zhi-ming
ZM
Shao
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
D047629:Estrogen Receptor beta; D016209:Interleukin-8; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C065788:transcription factor PEA3; C508053:ERBB2 protein, human