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.
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.
Ren
Meng
M
Shandong Provincial Hospital, Shandong University, Jinan 250021, China.
Zhong
Xia
X
Ma
Chun-yan
CY
Sun
Ying
Y
Guan
Qing-Bo
QB
Cui
Bin
B
Guo
Jun
J
Wang
Hai
H
Gao
Ling
L
Zhao
Jia-jun
JJ
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*
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