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

Chia Huei Lee, Szu Han Lin, Shwu Fen Chang, Po Yuan Chang, Zhi Ping Yang, Shao Chun Lu

Research output: Contribution to journalArticle

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalOncology Reports
Issue number1
Publication statusPublished - Jul 2013



  • Cancer
  • ERK2
  • G-CSF
  • MAPK
  • MEK

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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