title: Regulation of CXCL8/IL-8 expression by zonula occludens-1 in human breast cancer cells.
abstract: Accumulating data now suggest that ZO-1, once delocalized from tight junctions, could be implicated in the regulation of tumor-promoting genes. Because of their major implication in different steps of tumor progression, we investigated here the influence of ZO-1 on chemokines expression in breast cancer cells. Using GeneArray analysis to compare chemokine mRNA expression in breast tumor cells transfected with a siRNA against ZO-1, we identified CXCL-8IL-8 as a major potential target of ZO-1 signaling, being strongly downregulated following ZO-1 siRNA transfection. Examining further the relationship between ZO-1 and interleukin-8 (CXCL8/IL-8), we first showed that CXCL8/IL-8 expression correlates with a relocalization of ZO-1 in several breast cancer cell lines. Moreover, CXCL8/IL-8 is downregulated in invasive BT549 cells transfected with three different ZO-1 siRNA and overexpressed in noninvasive BT20 and SKBR3 cells transfected with vectors expressing ZO-1. We also provide evidence for an activation of the CXCL8/IL-8 promoter by ZO-1. Finally, we show that the regulation of CXCL8/IL-8 by ZO-1 is independent of the β-catenin pathway. Our results thus clearly show an implication of ZO-1 in CXCL8/IL-8 regulation. Because of the major implications of CXCL8/IL-8 in tumor invasion, such a regulation could play an important role in breast cancer progression.
authors: Laboratory of Developmental and Tumor Biology, GIGA-Cancer, University of Liège, Sart-Tilman, Liège, Belgium.
authors: Anne
authors: A
authors: Brysse
authors: Mélanie
authors: M
authors: Mestdagt
authors: Myriam
authors: M
authors: Polette
authors: Emilie
authors: E
authors: Luczka
authors: Walter
authors: W
authors: Hunziker
authors: Agnès
authors: A
authors: Noël
authors: Philippe
authors: P
authors: Birembaut
authors: Jean-Michel
authors: JM
authors: Foidart
authors: Christine
authors: C
authors: Gilles
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D062826:Zonula Occludens-1 Protein
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D008565:Membrane Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein