American Journal of Cancer Prevention
ISSN (Print): 2328-7314 ISSN (Online): 2328-7322 Website: Editor-in-chief: Nabil Abdel-Hamid
Open Access
Journal Browser
American Journal of Cancer Prevention. 2015, 3(6), 117-121
DOI: 10.12691/ajcp-3-6-3
Open AccessArticle

Effects of Mfn2 Gene Overexpression on EGFR Expression and Angiogenesis of a Heterologous Graft Model for Human Breast Infiltrating Duct Carcinoma in Nude Mice

Hu Ji-wei1, Yan Jin-yin1, Wang Ya-qi1, 2, Zhang Jing-hua1, 2, , Wang Lei3, Li Yu-feng4, Liu Yan4, 5, Ma Jie1, Li Ning1, Zhang Shun-li1, Gu Zheng1 and Wang Hong1

1Department of Surgical Oncology, Tangshan People's Hospital, Tangshan, China

2Department of Oncology, North China University of Science and Technology, Tangshan, China

3Department of Pathology, Tangshan People's Hospital, Tangshan, China

4Cancer Institute, Tangshan People’s Hospital, Tangshan, China

5College of Life Science, North China University of Science and Technology, Tangshan, China

Pub. Date: December 02, 2015

Cite this paper:
Hu Ji-wei, Yan Jin-yin, Wang Ya-qi, Zhang Jing-hua, Wang Lei, Li Yu-feng, Liu Yan, Ma Jie, Li Ning, Zhang Shun-li, Gu Zheng and Wang Hong. Effects of Mfn2 Gene Overexpression on EGFR Expression and Angiogenesis of a Heterologous Graft Model for Human Breast Infiltrating Duct Carcinoma in Nude Mice. American Journal of Cancer Prevention. 2015; 3(6):117-121. doi: 10.12691/ajcp-3-6-3


Objective: To investigate the antitumor angiogenesis activity of Mfn2 gene on a heterologous graft model for human breast infiltrating duct carcinoma in nude mice. To investigate the relationship between Mfn2 gene and Epidermal Growth Factor Receptor (EGFR). Methods: Human breast cancer MCF-7 cells steady infected with Mfn2 gene had been constructed. Western blotting was used to detect the overexpression of Mfn2 protein. Then the MCF-7 cells were injected subcutaneously into the breast pad of nude mice. Tumorigenicity and the growth of transplanted tumor in nude mice were observed. Growth curves were plotted based on mean tumor volume in each experimental group at the indicated time points. Meanwhile, the negative control group (NC group) which MCF-7 cells steady infected with PEGFP-N1 was set up. The expression of CD34 (reflect the microvessel density of tumor) and EGFR were detected by immunocytochemistry. Results: The tumor volume of the experimental group was smaller than the negative control group.The expression of CD34 of the experimental group was lower than the negative control group. The experimental group expressed low level of EGFR. Conclusion: Mfn2 significantly inhibits the growth of human breast cancer xenograft in nude mice. Downregulation of EGFR expression and decrease the potential of angiogenesis may be the potential mechanism.

breast cancer EGFR Mfn2 nude mice

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


Figure of 5


[1]  Group, E.B.C.T.C., Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. The Lancet, 2015.
[2]  Coates, A., et al., Tailoring therapies-improving the management of early breast cancer: St GallenInternational Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Annals of Oncology, 2015: p. mdv221.
[3]  Choi, B.O., et al., A cohort study of MFN2 mutations and phenotypic spectrums in Charcot–Marie–Tooth disease 2A patients. Clinical genetics, 2015. 87(6): p. 594-598.
[4]  Santel, A. and M.T. Fuller, Control of mitochondrial morphology by a human mitofusin. Journal of cell science, 2001. 114(5): p. 867-874.
[5]  de Brito, O.M. and L. Scorrano, Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature, 2008. 456(7222): p. 605-610.
[6]  Chen, K.-H., et al., Dysregulation of HSG triggers vascular proliferative disorders. Nature cell biology, 2004. 6(9): p. 872-883.
[7]  Wang, W., et al., Pro-apoptotic and anti-proliferative effects of mitofusin-2 via Bax signaling in hepatocellular carcinoma cells. Medical Oncology, 2012. 29(1): p. 70-76.
[8]  Jin, B., et al., Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma. Medical Oncology, 2011. 28(1): p. 373-380.
[9]  Wu, L., et al., Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells. Molecular cancer therapeutics, 2008. 7(1): p. 222-232.
[10]  Nuciforo, P., et al., Benefit to neoadjuvant anti–Human Epidermal Growth Factor Receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status. Annals of Oncology, 2015: p. mdv175.
[11]  Jiang, A., et al., Anti-Compression and Anti-Angiogenic Therapy for Breast Cancer. The FASEB Journal, 2015. 29(1 Supplement): p. 284.2.
[12]  Sledge, G.W., Anti–Vascular Endothelial Growth Factor Therapy in Breast Cancer: Game Over? Journal of Clinical Oncology, 2015. 33(2): p. 133-135.
[13]  Samoli, E., et al., Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk. Annals of Oncology, 2015. 26(4): p. 793-797.
[14]  Bosch, A., et al., PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor–positive breast cancer. Science translational medicine, 2015. 7(283): p. 283ra51-283ra51.
[15]  De Brito, O.M. and L. Scorrano, Mitofusin 2: a mitochondria-shaping protein with signaling roles beyond fusion. Antioxidants & redox signaling, 2008. 10(3): p. 621-634.
[16]  Westermann, B., Molecular machinery of mitochondrial fusion and fission. Journal of Biological Chemistry, 2008. 283(20): p. 13501-13505.
[17]  Arruda, A.P. and G.S. Hotamisligil, Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes. Cell metabolism, 2015.
[18]  Züchner, S., et al., Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nature genetics, 2004. 36(5): p. 449-451.
[19]  Baloh, R.H., et al., Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. The Journal of neuroscience, 2007. 27(2): p. 422-430.
[20]  Tufano, M., et al., Early onset Charcot‐Marie‐Tooth neuropathy type 2A and severe developmental delay: expanding the clinical phenotype of MFN2‐related neuropathy. Journal of the Peripheral Nervous System, 2015.
[21]  Sorianello, E., et al., The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells. Cardiovascular research, 2012: p. cvs006.
[22]  Wang, W., et al., HSG provides antitumor efficacy on hepatocellular carcinoma both in vitro and in vivo. Oncology reports, 2010. 24(1): p. 183-188.
[23]  Zhang, G.-E., et al., Anti-tumor effects of mfn2 in gastric cancer. International journal of molecular sciences, 2013. 14(7): p. 13005-13021.
[24]  Hu, X., et al., Lentivirus vector‑mediated mitofusin‑2 overexpression in rat ovary changes endocrine function and promotes follicular development in vivo. Experimental and therapeutic medicine, 2014. 8(3): p. 731-736.
[25]  Petit, A., et al., Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. The American journal of pathology, 1997. 151(6): p. 1523.
[26]  Yen, L., et al., Differential regulation of tumor angiogenesis by distinct ErbB homo-and heterodimers. Molecular biology of the cell, 2002. 13(11): p. 4029-4044.
[27]  Ellis, L.M., Epidermal growth factor receptor in tumor angiogenesis. Hematology/oncology clinics of North America, 2004. 18(5): p. 1007-1021.
[28]  Arteaga, C.L. Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. in Seminars in oncology. 2002. Elsevier.
[29]  Tabernero, J., The role of VEGF and EGFR inhibition: implications for combining anti–VEGF and anti–EGFR agents. Molecular Cancer Research, 2007. 5(3): p. 203-220.
[30]  Hynes, N.E. and H.A. Lane, ERBB receptors and cancer: the complexity of targeted inhibitors. Nature Reviews Cancer, 2005. 5(5): p. 341-354.