title: MADD promotes the survival of human lung adenocarcinoma cells by inhibiting apoptosis.
abstract: 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.
authors: Institute of Biochemistry and Molecular Biology, School of Medicine, Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors: Wenxiang
authors: W
authors: Bi
authors: Yuping
authors: Y
authors: Wei
authors: Jinxiang
authors: J
authors: Wu
authors: Gaoying
authors: G
authors: Sun
authors: Yuanfang
authors: Y
authors: Guo
authors: Qiang
authors: Q
authors: Zhang
authors: Liang
authors: L
authors: Dong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human