Open AccessNGX6 expression improves the sensitivity of tamoxifen-resistant MCF-7 cells through modulation of the Smad signaling pathway
Author(s) -
Wenjing Zhao,
Ke Wang
Publication year - 2013
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2013.1886
Subject(s) - tamoxifen , oncogene , mcf 7 , smad , apoptosis , cancer research , breast cancer , western blot , cell cycle , biology , chemistry , signal transduction , medicine , cancer , microbiology and biotechnology , gene , biochemistry , human breast
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.