title: Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphatidylinositol 3-kinase/nuclear factor-kappaB signaling pathway in FRTL thyroid cells.
abstract: OBJECTIVE
  Insulin-like growth factor-1 (IGF-1) is an important hypertrophic and cell cycle progression factor for a number of cell types. It has been proven that IGF-1 is involved in the regulation of thyroid proliferation and cell cycle progression; however, the exact mechanism of this regulation has not been fully elucidated. In the present study, we investigated the effect of IGF-1 on the expression of cyclin D1, an important cell cycle regulatory protein, and a signaling pathway involved in IGF-1's effect on cyclinD1 expression in FRTL thyroid cells.
  
  
  METHODS
  FRTL thyroid cells were treated with IGF-1 or vector control for 24 h. As appropriate to individual experiments, a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and/or a nuclear factor-kappaB (NF-kappaB) inhibitor, BAY11-7082, were added 1 h prior to IGF-1 treatment. Western blotting was used to detect cyclin D1 protein expression. Immunofluorescence was performed to analyze the expression of IkappaBalpha, an NF-kappaB inhibitory protein. Cell cycle analysis was performed by fluorescence activated cell sorting (FACS).
  
  
  RESULTS
  IGF-1 increased the cyclin D1 expression in thyroid cells. This increase was blocked by pretreatment with LY294002 or BAY11-7082. Further studies showed that IGF-1 specifically induced NF-kappaB activity. Treatment with IGF-1 could accelerate cell cycle progression from G(0)/G(1) to S phase, whereas this progression was inhibited by the presence of LY294002 or BAY11-7082.
  
  
  CONCLUSIONS
  In summary, the results of the present study show that in FRTL cells, IGF-1 promotes cell cycle progression via an upregulation of cyclin D1 expression, at least partially through the PI3K/NF-kappaB signaling pathway.
authors.affiliation: Shandong Provincial Hospital, Shandong University, Jinan 250021, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.forename: Xia
authors.initials: X
authors.lastname: Zhong
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Guan
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jia-jun
authors.initials: JJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002867:Chromones / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009025:Morpholines / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013450:Sulfones / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology*
chemical_list: D002867:Chromones; D019938:Cyclin D1; D007334:Insulin-Like Growth Factor I; D009025:Morpholines; D016328:NF-kappa B; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013450:Sulfones; C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one