MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis
Autor: | Gaoying Sun, Jinxiang Wu, Qiang Zhang, Wenxiang Bi, Yuping Wei, Liang Dong, Yuanfang Guo |
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Rok vydání: | 2013 |
Předmět: |
Death Domain Receptor Signaling Adaptor Proteins
Cancer Research Lung Neoplasms Cell Survival Cell Adenocarcinoma of Lung Apoptosis Adenocarcinoma Biology Cell Line Tumor medicine Guanine Nucleotide Exchange Factors Humans Molecular Targeted Therapy Cell Proliferation A549 cell Oncogene Cell growth General Medicine Transfection respiratory system Cell cycle medicine.disease respiratory tract diseases Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cancer research |
Zdroj: | Oncology Reports. 29:1533-1539 |
ISSN: | 1791-2431 1021-335X |
Popis: | MAPK-activating death domain protein (MADD) binds to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor and acts as a key downstream mediator in the TRAIL-induced apoptosis pathway. The aim of this study was to evaluate the expression of MADD in normal human and adenocarcinoma tissues of the lungs and its influence on proliferation and apoptosis of A549 human lung adenocarcinoma cells. Immunohistochemistry was carried out to detect the expression of MADD in normal and tumor tissues of the lungs. Expression of the MADD gene in A549 cells was measured by reverse transcription-polymerase chain reaction. A549 cells were transfected with plasmids carrying the DNA fragment encoding MADD and lentiviral vectors used for RNA interference, respectively. MADD expression in the transfected A549 cells was determined by western blotting. Proliferation and apoptosis were detected using MTT assay and flow cytometry, respectively. It was found that non-small cell lung cancer tissues expressed MADD at higher levels compared to normal lung tissues, and the level of MADD in lung adenocarcinoma was higher compared to that in lung squamous cell carcinoma. MADD was expressed in A549 cells. Both introduction of the DNA fragment encoding MADD and RNA interference targeting MADD effectively altered levels of MADD in the A549 cells. Overexpression of MADD in the A549 cells inhibited apoptosis and increased survival whereas abrogation of MADD promoted apoptosis and reduced cell proliferation. These results suggest that MADD may be a potential therapeutic target for lung adenocarcinoma therapy involving the TRAIL-induced apoptosis pathway. |
Databáze: | OpenAIRE |
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