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Overexpression of mitochondrial ferritin inhibited the tumour cell proliferation by regulation of cellular iron mechanism and the expression of cyclins
SHI Fang-fang ZHANG Na GUAN Peng GAO Zhi-guo FAN Jing-qi CHANG Yan-zhong SHI Zhen-hua* DUAN Xiang-lin
Acta Anatomica Sinica ›› 2013, Vol. 44 ›› Issue (2) : 214-218.
Overexpression of mitochondrial ferritin inhibited the tumour cell proliferation by regulation of cellular iron mechanism and the expression of cyclins
Objective To study the mechanism of overexpression of mitochondrial ferritin(MtFt) for inhibiting neuroblastoma cell proliferation. Method MtFt-SY5Y cells were selected as the experimental model and SH-SY5Y and pcDNA3.1-SY5Y cells were used as control group. The effects of overexpression of MtFt on SH-SY5Y cells proliferation, iron metabolism related protein transferrin receptor1(TfR1) and ferritin, cyclins(cyclinD1, cyclinE ) and cyclin dependant kinases (CDK2, CDK4) were tested by flow cytometry and Western bloting. Result Overexpression of MtFt inhibited markedly tumour cell proliferation by regulation of iron metabolism and the expression of cyclins and cyclin dependant kinase. The proliferation speed of MtFt-SY5Y cells was 4 times slower than that of the control group. MtFt caused the cytoplasm iron deficiency and transferrin receptor1(TfR1) upregulation, and H-ferritin downregulation markedly respectively. Meanwhile, cyclinD1 and CDK2 downregulated significantly and cyclinE upregulated significantly. The expression of CDK4 decreased but no significant difference compared with control group. Conclusion Overexpression of MtFt inhibits the tumour cell proliferation markedly. The mechanism may be caused by regulation of cellular iron metabosism and the expression of cyclins and cyclin dependent kinase (CDK) which further arrest cell cycle.
Mitochondrial ferritin / Iron metabolism / Cell proliferation / Cyclin / Flow cytometry / Western blotting
[1] Nurtjahja-Tjendraputra E, Fu D, Phang JM, et al. Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression[J]. Blood, 2007, 109(9): 4045-4054.
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