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EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway

  • Authors:
    • Sung Lyea Park
    • Se Yeon Won
    • Jun-Hui Song
    • Wun-Jae Kim
    • Sung-Kwon Moon

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  • Published online on: August 20, 2014     https://doi.org/10.3892/or.2014.3428
  • Pages: 2207-2214
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Abstract

Erythropoietin (EPO) is a cytokine that modulates the production of red blood cells. Previous studies have contradicted the assumed role of EPO in tumor cell proliferation. In the present study, we investigated the effect of EPO in the proliferation, migration and invasion that is involved in the signaling pathways and cell-cycle regulation of bladder cancer 5637 cells. The results showed that an overexpression of the EPO gene has a potent stimulatory effect on DNA synthesis, migration and invasion. EPO gene expression increased the expression of matrix metalloproteinase (MMP)-9 via the binding activity of NF-κB, AP-1 and Sp-1 in 5637 cells. The transfection of 5637 cells with the EPO gene induced the phosphorylation of ERK1/2. Treatment with ERK1/2 inhibitor U0126 significantly inhibited the increased proliferation, migration and invasion of EPO gene-transfected cells. U0126 treatment suppressed the induction of MMP-9 expression through NF-κB binding activity in EPO gene transfectants. In addition, EPO gene expression was correlated with the upregulation of cyclins/CDKs and the upregulation of the CDK inhibitor p21WAF1 expression. Finally, the inhibition of p21WAF1 function by siRNA blocked the proliferation, migration, invasion and phosphorylation of ERK1/2 signaling, as well as MMP-9 expression and activation of NF-κB in EPO gene-transfected cells. These novel findings suggest that the molecular mechanisms of EPO contribute to the progression and development of bladder tumors.
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November-2014
Volume 32 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 4.2
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  • CiteScore: 8.4
  • CiteScore Rank: Q1: #68/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.786
  • SCImago Journal Rank (SJR): 0.812
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Spandidos Publications style
Park SL, Won SY, Song J, Kim W and Moon S: EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway. Oncol Rep 32: 2207-2214, 2014
APA
Park, S.L., Won, S.Y., Song, J., Kim, W., & Moon, S. (2014). EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway. Oncology Reports, 32, 2207-2214. https://doi.org/10.3892/or.2014.3428
MLA
Park, S. L., Won, S. Y., Song, J., Kim, W., Moon, S."EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway". Oncology Reports 32.5 (2014): 2207-2214.
Chicago
Park, S. L., Won, S. Y., Song, J., Kim, W., Moon, S."EPO gene expression induces the proliferation, migration and invasion of bladder cancer cells through the p21WAF1‑mediated ERK1/2/NF-κB/MMP-9 pathway". Oncology Reports 32, no. 5 (2014): 2207-2214. https://doi.org/10.3892/or.2014.3428