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Article

Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells

  • Authors:
    • Li Ma
    • Yuan Chang
    • Long Yu
    • Wenbo He
    • Yueping Liu
  • View Affiliations / Copyright

    Affiliations: Breast Disease Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
  • Pages: 3816-3822
    |
    Published online on: September 25, 2015
       https://doi.org/10.3892/ol.2015.3748
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Abstract

The mitochondrial GTPase mitofusin‑2 (Mfn2) gene is a novel gene characterized as a cell proliferation inhibitor. Mfn2 has previously been reported to play a role in regulating cell proliferation, apoptosis and differentiation in a number of cell types. However, there are no studies on the effect of Mfn2 in breast cancer. In this study, we aimed to elucidate the function and mechanism of Mfn2 in breast cancer. A plasmid encoding the complete Mfn2 open reading frame (pEGFP‑Mfn2) was used to infect breast cancer cells. The effect of Mfn2 on proliferation was assessed by methyl thiazolyl tetrazolium and bromodeoxyuridine incorporation analyses. Flow cytometry, immunofluorescence and western blot analyses were used to test the effects of Mfn2 on cell cycle distribution and apoptosis. Additionally, the PI3K/Akt signaling pathway was analyzed after pEGFP‑Mfn2 was transfected into MCF‑7 cells. The results revealed that Mfn2 suppressed the proliferation of MCF‑7 cells by regulating more cells at the G0/G1 phase and decreasing proliferating cell nuclear antigen and cyclin A expression. The results also demonstrated that the PI3K/Akt signaling pathway is involved in Mfn2‑regulated proliferation and apoptosis. Taken together, this indicates that Mfn2 mediates MCF‑7 cell proliferation and apoptosis via the PI3K/Akt signaling pathway. Mfn2 may thus be a significant therapeutic target in the treatment of breast cancer.
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1 

Chen G, Liu N, Zhou A, Tang C, Ma D and Tang J: The role of hypertension-related gene in aortic vascular smooth muscle cells from mice and rats. Chin Med J (Engl). 114:833–836. 2001.PubMed/NCBI

2 

Guo X, Chen KH, Guo Y, et al: Mitofusin 2 triggers vascular smooth muscle cell apoptosis via mitochondrial death pathway. Circ Res. 101:1113–1122. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Karbowski M, Lee YJ, Gaume B, Jeong SY, Frank S, Nechushtan A, Santel A, Fuller M, Smith CL and Youle RJ: Spatial and temporal association of Bax with mitochondrial fission sites, Drp1 and Mfn2 during apoptosis. J Cell Biol. 159:931–938. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Chen KH, Guo X, Ma D, Guo Y, Li Q, Yang D, Li P, Qiu X, Wen S, Xiao RP and Tang J: Dysregulation of HSG triggers vascular proliferative disorders. Nat Cell Biol. 6:872–883. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Wang W, Lu J, Zhu F, Wei J, Jia C, Zhang Y, Zhou L, Xie H and Zheng S: Pro-apoptotic and anti-proliferative effects of mitofusin-2 via Bax signaling in hepatocellular carcinoma cells. Med Oncol. 29:70–76. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Jin B, Fu G, Pan H, Cheng X, Zhou L, Lv J, Chen G and Zheng S: Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma. Med Oncol. 28(Suppl 1): S373–S380. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Zhang GE, Jin HL, Lin XK, Chen C, Liu XS, Zhang Q and Yu JR: Anti-tumor effects of mfn2 in gastric cancer. Int J Mol Sci. 14:13005–13021. 2013. View Article : Google Scholar : PubMed/NCBI

8 

MacGregor JI and Jordan VC: Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev. 50:151–196. 1998.PubMed/NCBI

9 

Sommer S and Fuqua SA: Estrogen receptor and breast cancer. Semin Cancer Biol. 11:339–352. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Nilsson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M and Gustafsson JA: Mechanisms of estrogen action. Physiol Rev. 81:1535–1565. 2001.PubMed/NCBI

11 

Speirs V, Carder PJ, Lane S, Dodwell D, Lansdown MR and Hanby AM: Oestrogen receptor beta: what it means for patients with breast cancer. Lancet Oncol. 5:174–181. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Ma L, Liu Y, Geng C, Qi X and Jiang J: Estrogen receptor β inhibits estradiol-induced proliferation and migration of MCF-7 cells through regulation of mitofusin 2. Int J Oncol. 42:1993–2000. 2013.PubMed/NCBI

13 

Zhang D, Ma C, Li S, Ran Y, Chen J, Lu P, Shi S and Zhu D: Effect of Mitofusin 2 on smooth muscle cells proliferation in hypoxic pulmonary hypertension. Microvasc Res. 84:286–296. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Fabregat I, Roncero C and Fernandez M: Survival and apoptosis: A dysregulated balance in liver cancer. Liver Int. 27:155–162. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Guicciardi ME and Gores GJ: Apoptosis: A mechanism of acute and chronic liver injury. Gut. 54:1024–1033. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Braathen GJ, Sand JC, Lobato A, Høyer H and Russell MB: Mfn2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families. BMC Med Genet. 11:482010. View Article : Google Scholar : PubMed/NCBI

17 

Bagchi A and Mills AA: The quest for the 1p36 tumor suppressor. Cancer Res. 68:2551–2556. 2008. View Article : Google Scholar : PubMed/NCBI

18 

de Brito OM and Scorrano L: Mitofusin 2: A mitochondria-shaping protein with signaling roles beyond fusion. Antioxid Redox Signal. 10:621–633. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Westermann B: Molecular machinery of mitochondrial fusion and fission. J Biol Chem. 283:13501–13505. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Hirai K, Hayashi T, Chan PH, Zeng J, Yang GY, Basus VJ, James TL and Litt L: PI3K inhibition in neonatal rat brain slices during and after hypoxia reduces phospho-Akt and increases cytosolic cytochrome c and apoptosis. Brain Res Mol Brain Res. 124:51–61. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Saini KS, Loi S, de Azambuja E, Metzger-Filho O, Saini ML, Ignatiadis M, Dancey JE and Piccart-Gebhart MJ: Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev. 39:935–946. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Yi YW, Hong W, Kang HJ, Kim HJ, Zhao W, Wang A, Seong YS and Bae I: Inhibition of the PI3K/AKT pathway potentiates cytotoxicity of EGFR kinase inhibitors in triple-negative breast cancer cells. J Cell Mol Med. 17:648–656. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Pande S, Browne G, Padmanabhan S, Zaidi SK, Lian JB, van Wijnen AJ, Stein JL and Stein GS: Oncogenic cooperation between PI3K/Akt signaling and transcription factor Runx2 promotes the invasive properties of metastatic breast cancer cells. J Cell Physiol. 228:1784–1792. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Calleros L, Sánchez-Hernández I, Baquero P, Toro MJ and Chiloeches A: Oncogenic Ras, but not (V600E) B-RAF, protects from cholesterol depletion-induced apoptosis through the PI3K/AKT pathway in colorectal cancer cells. Carcinogenesis. 30:1670–1677. 2009. View Article : Google Scholar : PubMed/NCBI

25 

De Luca A, Maiello MR, D'Alessio A, Pergameno M and Normanno N: The RAS/RAF/MEK/ERK and the PI3K/AKT signaling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets. 16(Suppl 2): S17–S27. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Tsubaki M, Satou T, Itoh T, Imano M, Ogaki M, Yanae M and Nishida S: Reduction of metastasis, cell invasion and adhesion in mouse osteosarcoma by YM529/ONO-5920-induced blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathway. Toxicol Appl Pharmacol. 259:402–410. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma L, Chang Y, Yu L, He W and Liu Y: Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells. Oncol Lett 10: 3816-3822, 2015.
APA
Ma, L., Chang, Y., Yu, L., He, W., & Liu, Y. (2015). Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells. Oncology Letters, 10, 3816-3822. https://doi.org/10.3892/ol.2015.3748
MLA
Ma, L., Chang, Y., Yu, L., He, W., Liu, Y."Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells". Oncology Letters 10.6 (2015): 3816-3822.
Chicago
Ma, L., Chang, Y., Yu, L., He, W., Liu, Y."Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells". Oncology Letters 10, no. 6 (2015): 3816-3822. https://doi.org/10.3892/ol.2015.3748
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Chang Y, Yu L, He W and Liu Y: Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells. Oncol Lett 10: 3816-3822, 2015.
APA
Ma, L., Chang, Y., Yu, L., He, W., & Liu, Y. (2015). Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells. Oncology Letters, 10, 3816-3822. https://doi.org/10.3892/ol.2015.3748
MLA
Ma, L., Chang, Y., Yu, L., He, W., Liu, Y."Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells". Oncology Letters 10.6 (2015): 3816-3822.
Chicago
Ma, L., Chang, Y., Yu, L., He, W., Liu, Y."Pro‑apoptotic and anti‑proliferative effects of mitofusin‑2 via PI3K/Akt signaling in breast cancer cells". Oncology Letters 10, no. 6 (2015): 3816-3822. https://doi.org/10.3892/ol.2015.3748
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