title: NGX6 expression improves the sensitivity of tamoxifen-resistant MCF-7 cells through modulation of the Smad signaling pathway.
abstract: The effects of nasopharyngeal carcinoma-associated gene 6 (NGX6) in breast cancer was studied. We demonstrated that the levels of the NGX6 protein and mRNA were lower in patients with tamoxifen-resistant tumors compared to patients with tamoxifen-sensitive tumors. Tamoxifen was able to decrease proliferation, increase apoptosis and induce G1 arrest in NGX6-expressing TRM-7 cells in vitro. In order to detect the mechanism(s) of tamoxifen action, we first obtain the three-dimensional structure of the NGX6 protein by using Protein Homology/analogY Recognition Engine (PHYRE). Prediction of the docking between the NGX6 protein and tamoxifen was performed using SYBYL-X 1.3. Furthermore, we found that tamoxifen activated Smad2/3, and increased the expression of Smad4 in NGX6-expressing TRM-7 cells as evaluated by western blot analysis. Smad2/3-targeted siRNA was used to confirm the mechanism(s) of tamoxifen action in NGX6-expressing cells. These results indicated that NGX6 may increase the sensitivity of breast cancer cells to tamoxifen.
authors.affiliation: Department of Ultrasound, Τhe First Affiliated Hospital of China Medical University, Heping District, Shenyang, Liaoning 110001, P.R. China. wenj_cmu@163.com
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Zhao
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism*; D013629:Tamoxifen / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008565:Membrane Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; C477325:TMEM8B protein, human; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen