title: IGF-1 mediates PTEN suppression and enhances cell invasion and proliferation via activation of the IGF-1/PI3K/Akt signaling pathway in pancreatic cancer cells.
abstract: BACKGROUND
  Type-1 insulin-like growth factor (IGF-1) up-regulates cell proliferation and invasiveness through activation of PI3K/Akt signaling pathway. IGF-1 also down-regulates the tumor suppressor chromosome 10 (PTEN). We investigated the mechanism by which IGF-1 affects cell proliferation and invasion by suppression of PTEN phosphorylation and interaction with PI3K/PTEN/Akt/NF-small ka, CyrillicB signaling pathway in pancreatic cancer.
  
  
  METHODS
  The expression of IGF-1 receptor (IGF-1R) and PTEN in five pancreatic cancer cell lines was determined by RT-PCR and Western blot. Proliferation and invasion were investigated by WST-1 assay and Matrigel-double chamber assay. Pancreatic cancer cells were transfected with PTEN siRNA to investigate which signaling pathway correlates in regulation of cancer cell proliferation and invasion.
  
  
  RESULTS
  Five pancreatic cancer cell lines expressed PTEN and IGF-1R in mRNA and protein levels. Suppression of PTEN phosphorylation strongly enhanced cell proliferation and invasion stimulated with IGF-1 via activation of PI3K/Akt/NF-small ka, CyrillicB signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-small ka, CyrillicB pathway, subsequently up-regulating cell invasiveness and proliferation.
  
  
  CONCLUSIONS
  The IGF-1/PI3K/PTEN/Akt/NF-small ka, CyrillicB cascade may be a key pathway stimulating metastasis of pancreatic cancer cells. We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-small ka, CyrillicB might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.
authors: Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors: Jiachi
authors: J
authors: Ma
authors: Hirozumi
authors: H
authors: Sawai
authors: Yoichi
authors: Y
authors: Matsuo
authors: Nobuo
authors: N
authors: Ochi
authors: Akira
authors: A
authors: Yasuda
authors: Hiroki
authors: H
authors: Takahashi
authors: Takehiro
authors: T
authors: Wakasugi
authors: Hitoshi
authors: H
authors: Funahashi
authors: Mikinori
authors: M
authors: Sato
authors: Hiromitsu
authors: H
authors: Takeyama
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human