Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells

  • Authors:
    • Chia-Huei Lee
    • Szu-Han Lin
    • Shwu-Fen Chang
    • Po-Yuan Chang
    • Zhi-Ping Yang
    • Shao-Chun Lu
  • View Affiliations

  • Published online on: May 14, 2013     https://doi.org/10.3892/or.2013.2463
  • Pages: 419-424
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Abstract

Granulocyte colony-stimulating factor (G-CSF) affects granulopoiesis and is important for mobilizing neutrophils into blood circulation. Due to the hematopoietic properties of G-CSF, it has been widely used to clinically treat chemotherapy-induced neutropenia. However, G-CSF can promote tumors by inhibiting innate and adaptive immunity and enhancing angiogenesis and neoplastic growth. Most G-CSF-producing tumors are associated with a poor prognosis. This indicates that G-CSF promotes cancer progression. Thus, identifying regulatory molecules involved in tumor-derived G-CSF expression may provide therapeutic targets for cancer treatment. This study identified considerable G-CSF expression in malignant breast, lung and oral cancer cells. However, G-CSF expression was barely detectable in non-invasive cell lines. Expression of G-CSF mRNA and protein increased during exposure to tumor necrosis factor-α (TNF-α). Treatment with U0126 (a mitogen-activated protein kinase inhibitor) drastically reduced basal levels of G-CSF and TNF-α-induced G-CSF in aggressive cancer cells. This study also showed that knockdown of extracellular signal-regulated kinase (ERK) 2 by shRNA was necessary and sufficient to eliminate the expression of tumor-derived G-CSF. This did not apply to ERK1. Therefore, ERK2 (but not ERK1) is responsible for the transcriptional regulation of tumor-derived G-CSF. The results indicate the pharmaceutical value of specific ERK2 inhibitors in treating patients with G-CSF-producing tumors.
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July 2013
Volume 30 Issue 1

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

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Spandidos Publications style
Lee C, Lin S, Chang S, Chang P, Yang Z and Lu S: Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells. Oncol Rep 30: 419-424, 2013
APA
Lee, C., Lin, S., Chang, S., Chang, P., Yang, Z., & Lu, S. (2013). Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells. Oncology Reports, 30, 419-424. https://doi.org/10.3892/or.2013.2463
MLA
Lee, C., Lin, S., Chang, S., Chang, P., Yang, Z., Lu, S."Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells". Oncology Reports 30.1 (2013): 419-424.
Chicago
Lee, C., Lin, S., Chang, S., Chang, P., Yang, Z., Lu, S."Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells". Oncology Reports 30, no. 1 (2013): 419-424. https://doi.org/10.3892/or.2013.2463