Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells
Resource
Oncol. Rep., 30(1), 419-424
Journal
Oncology Reports
Pages
419-424
Date Issued
2013
Date
2013
Author(s)
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-alpha (TNF-alpha). Treatment with U0126 (a mitogen-activated protein kinase inhibitor) drastically reduced basal levels of G-CSF and TNF-alpha-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.
Subjects
G-CSF
cancer
MAPK
MEK
ERK2
SDGs
Other Subjects
1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; granulocyte colony stimulating factor; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; short hairpin RNA; tumor necrosis factor alpha; antineoplastic activity; article; breast cancer; cancer cell culture; cancer growth; carcinogenesis; cell level; controlled study; gene expression; gene silencing; human; human cell; lung cancer; malignant neoplastic disease; mouth cancer; priority journal; protein analysis; protein expression; protein function; transcription regulation; Adenocarcinoma; Breast Neoplasms; Butadienes; Carcinoma, Squamous Cell; Cell Line, Tumor; Enzyme Inhibitors; Female; Gene Expression Regulation, Neoplastic; Granulocyte Colony-Stimulating Factor; Humans; Lung Neoplasms; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasms; Nitriles; RNA Interference; RNA, Messenger; RNA, Small Interfering; Tumor Necrosis Factor-alpha
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