https://scholars.lib.ntu.edu.tw/handle/123456789/190528
標題: | Extracellular signal-regulated kinase 2 mediates the expression of granulocyte colony-stimulating factor in invasive cancer cells | 作者: | Lee C.-H. Lin S.-H. Chang S.-F. PO-YUAN CHANG Yang Z.-P. SHAO-CHUN LU |
關鍵字: | G-CSF;cancer;MAPK;MEK;ERK2 | 公開日期: | 2013 | 起(迄)頁: | 419-424 | 來源出版物: | Oncology Reports | 摘要: | 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. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/259412 | DOI: | 10.3892/or.2013.2463 | SDG/關鍵字: | 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 |
顯示於: | 醫學系 |
檔案 | 描述 | 大小 | 格式 | |
---|---|---|---|---|
index.html | 23.16 kB | HTML | 檢視/開啟 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。