title: PI3K/Akt and MAPK/ERK1/2 signaling pathways are involved in IGF-1-induced VEGF-C upregulation in breast cancer.
abstract: OBJECTIVE
  To investigate the signaling pathways involved in insulin-like growth factor-1 (IGF-1)-induced vascular endothelial growth factor C (VEGF-C) up-regulation and lymphatic metastasis in MDA-MB-231 breast cancer cells.
  
  
  METHODS
  MDA-MB-231 breast cancer cells were exposed to IGF-1 with various concentrations. The expression level of VEGF-C was assessed by real-time PCR and Western blot. Akt and ERK1/2 phosphorylation was detected by Western blot. Signaling transduction inhibitors, LY294002 and PD98059, were used to block PI3K/Akt and MAPK/ERK1/2 signaling pathways, respectively.
  
  
  RESULTS
  IGF-1 increased the level of VEGF-C expression in a dose-dependent manner in MDA-MB-231 breast cancer cells. In addition, phosphorylation of Akt and ERK1/2 was enhanced by IGF-1. Remarkably, inhibition of Akt phosphorylation by LY294002 completely blocked the effects on IGF-1-induced VEGF-C up-regulation. Inhibition of ERK1/2 phosphorylation by PD98059 reduced IGF-1-induced VEGF-C expression.
  
  
  CONCLUSIONS
  This study identified that PI3K/Akt and MAPK/ERK1/2 signaling pathways were involved in IGF-1-induced VEGF-C up-regulation and suggested their important roles in lymphatic metastasis in breast cancer.
authors: Department of General Surgery, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors: Chenfang
authors: C
authors: Zhu
authors: Xiaoliang
authors: X
authors: Qi
authors: Yaning
authors: Y
authors: Chen
authors: Bo
authors: B
authors: Sun
authors: Yalei
authors: Y
authors: Dai
authors: Yan
authors: Y
authors: Gu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System / Q000235:genetics*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism
chemical_list: D002867:Chromones; D009025:Morpholines; D042582:Vascular Endothelial Growth Factor C; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt