Tumor Biology

, Volume 37, Issue 5, pp 6053–6063 | Cite as

Regulatory effects of ΔFosB on proliferation and apoptosis of MCF-7 breast cancer cells

  • Hui Li
  • Lihui Li
  • Huiling Zheng
  • Xiaotong Yao
  • Wenjuan Zang
Original Article

Abstract

Matrix metalloproteinase-9 (MMP-9) plays a vital role in tumor angiogenesis, cell migration, and invasiveness because it can degrade almost all basement membrane and extracellular matrix components. MMP-9 has been reported in many cancers including breast cancer, lung cancer, and colon cancer. ΔFosB in mammary epithelial cells has been shown to regulate cell proliferation, differentiation, and death. We found that ΔFosB increased the expression of MMP-9 in MCF-7 breast cancer cells. ΔFosB overexpression in MCF-7 cells increased cellular viability and decreased cell apoptosis. SB-3CT, an inhibitor of MMP-9, promoted apoptosis, inhibited cell proliferation, induced cell cycle arrest, and downregulated the expression of antiapoptotic genes Bcl-2 and Bcl-xl in MCF-7 cells. ΔFosB increased the number of MCF-7 cells in G2/M and S phases, upregulated the expression of Bcl-2 and Bcl-xl, and protected MCF-7 cells from apoptosis induced by MMP-9 inhibition. We also found that ΔFosB overexpression in MCF-7 cells inhibited Ca2+-induced apoptosis and promoted cell proliferation. Therefore, ΔFosB may be a potential target in breast cancer cell apoptosis by regulating the expression of MMP-9.

Keywords

MMP-9 ΔFosB Breast cancer Proliferation Apoptosis 

Notes

Acknowledgments

This work was supported by the “National Natural Science Foundation of China (No. 31572368)” and “Special Fund for Agro-scientific Research in the Public Interest (No.201103038)”.

Compliance with ethical standards

Conflicts of interest

None.

Supplementary material

13277_2015_4356_Fig10_ESM.gif (22 kb)
Fig. S1

ΔFosB increases MMP-9 expression in cultured MCF-7 breast cancer cells. The MCF-7 cells were transduced with ΔFosB interference recombinant adenoviruses Ad-ΔFosB-572 for 24 h and subsequently were transduced with overexpression recombinant adenoviruses Ad-ΔFosB for 48 h. MMP-9 mRNA levels were analyzed by quantitative real-time PCR (RT-qPCR). Values are means ± SEM (n = 3). *P<0.05; **P<0.01; *** P<0.001. Ad-ΔFosB the overexpression recombinant adenoviruses of ΔFosB, Ad-ΔFosB-572 the interference recombinant adenoviruses of ΔFosB. (GIF 21 kb)

13277_2015_4356_MOESM1_ESM.tif (102 kb)
High Resolution (TIF 102 kb)
13277_2015_4356_Fig11_ESM.gif (45 kb)
Fig. S2

ΔFosB-dependent protection from SB-3CT-induced cell apoptosis in MCF-7 breast cancer cells. MCF-7 cells were transduced with Ad-ΔFosB or Ad-ΔFosB-572 for 48 h and subsequently exposed to different concentrations of SB-3CT for 24 h. Cell apoptosis was determined by Annexin V-FITC/PI binding followed by flow cytometry. Values are means ± SEM (n = 3). *P<0.05; **P<0.01; *** P<0.001. Ad-ΔFosB the overexpression recombinant adenoviruses of ΔFosB, Ad-ΔFosB-572 the interference recombinant adenoviruses of ΔFosB, SB-3CT an inhibitor of MMP-9. (GIF 45 kb)

13277_2015_4356_MOESM2_ESM.tif (197 kb)
High Resolution (TIF 197 kb)
13277_2015_4356_Fig12_ESM.gif (50 kb)
Fig. S3

ΔFosB-dependent protection from Ca2+-induced cell apoptosis in MCF-7 breast cancer cells. MCF-7 cells were transduced with Ad-ΔFosB or Ad-ΔFosB-572 for 48 h, and subsequently exposed to different concentrations of Ca2+ for 24 h. Cell apoptosis was determined Annexin V-FITC/PI binding followed by flow cytometry. Values are means ± SEM (n = 3). *P<0.05; **P<0.01; *** P<0.001. Ad-ΔFosB the overexpression recombinant adenoviruses of ΔFosB, Ad-ΔFosB-572 the interference recombinant adenoviruses of ΔFosB. (GIF 49 kb)

13277_2015_4356_MOESM3_ESM.tif (542 kb)
High Resolution (TIF 541 kb)
13277_2015_4356_Fig13_ESM.gif (16 kb)
Fig. S4

The effects of Ca2+ on the mRNA expression of ΔFosB and MMP-9. MCF-7 cells were treated with different concentrations of Ca2+ for 24 h, and the mRNA levels of ΔFosB and MMP-9 were analyzed by quantitative real-time PCR (RT-qPCR). Values are means ± SEM (n = 3). *P<0.05; **P<0.01; *** P<0.001. (GIF 15 kb)

13277_2015_4356_MOESM4_ESM.tif (65 kb)
High Resolution (TIF 65 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Hui Li
    • 1
  • Lihui Li
    • 1
  • Huiling Zheng
    • 1
  • Xiaotong Yao
    • 1
  • Wenjuan Zang
    • 1
  1. 1.Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and TechnologyNorthwest A&F UniversityYanglingChina

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