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

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)419-424
Number of pages6
JournalOncology Reports
Volume30
Issue number1
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Mitogen-Activated Protein Kinase 1
Granulocyte Colony-Stimulating Factor
Neoplasms
Tumor Necrosis Factor-alpha
Blood Circulation
Mouth Neoplasms
Adaptive Immunity
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Neutropenia
Innate Immunity
Small Interfering RNA
Lung Neoplasms
Neutrophils

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells. / Lee, Chia Huei; Lin, Szu Han; Chang, Shwu Fen; Chang, Po Yuan; Yang, Zhi Ping; Lu, Shao Chun.

In: Oncology Reports, Vol. 30, No. 1, 07.2013, p. 419-424.

Research output: Contribution to journalArticle

Lee, Chia Huei ; Lin, Szu Han ; Chang, Shwu Fen ; Chang, Po Yuan ; Yang, Zhi Ping ; Lu, Shao Chun. / Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells. In: Oncology Reports. 2013 ; Vol. 30, No. 1. pp. 419-424.
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