title: Mesothelin promotes invasion and metastasis in breast cancer cells.
abstract: OBJECTIVE
  The presence of mesothelin (encoded by the mesothelin [MSLN] gene) in breast cancer is associated with tumour infiltration of the lymph node. This study evaluated whether MSLN overexpression promotes breast cancer cell invasiveness and metastasis.
  
  
  METHODS
  This study evaluated the effects of overexpression of MSLN on extracellular signal-regulated kinase (ERK1/2) and matrix metalloproteinase (MMP)-9 levels, and the invasiveness and angiogenesis of the breast cancer cell line MCF-7 in vitro, and on MCF-7-derived tumour development in vivo.
  
  
  RESULTS
  MSLN overexpression significantly increased ERK1/2 and MMP9 protein levels and activity, and the invasive and angiogenic capability of MCF-7 cells, in vitro. Inhibition of ERK1/2 suppressed MMP-9 and the invasive and angiogenic capability of MSLN overexpressing MCF-7 cells. MSLN overexpression also increased MCF-7-derived tumour metastasis in vivo.
  
  
  CONCLUSIONS
  MSLN overexpression promoted the invasive potential of MCF-7 cells through ERK1/2-dependent upregulation of MMP-9; this association may have contributed to metastasis of MCF-7 cells in vivo. Mesothelin may be a useful biomarker for cancer progression and a novel therapeutic or chemopreventive target in human breast cancer.
authors: Centre for Breast Diseases, The Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, China.
authors: Y
authors: Y
authors: Wang
authors: L
authors: L
authors: Wang
authors: D
authors: D
authors: Li
authors: H B
authors: HB
authors: Wang
authors: Q F
authors: QF
authors: Chen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D000090204:Mesothelin; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D009570:Nitriles / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014183:Transplantation, Heterologous
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D061965:Matrix Metalloproteinase Inhibitors; C000715528:Msln protein, mouse; D009570:Nitriles; D011480:Protease Inhibitors; D013876:Thiophenes; C113580:U 0126; D010649:Phenylalanine; C080985:batimastat; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9; D000090204:Mesothelin