title: Dominant negative epidermal growth factor receptor inhibits growth of human gastric cancer cells by inducing cell cycle arrest and apoptosis.
abstract: Epidermal growth factor receptor (EGFR) promotes proliferation of cancer cells. Dominant negative EGFR (DNEGFR) can block EGFR signal pathway by competing with endogenous EGFR for ligands. However, whether EGFR is overexpressed in gastric cancer and whether DNEGFR contributes to the inhibition of gastric cancer growth are not known. In this study, with the methods of immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry, Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling assay and western blotting; we demonstrate that EGFR is expressed in 29 of 60 of human gastric cancer. In addition, DNEGFR induces G0/G1 arrest by decreasing expression of phosphorylated retinoblastoma protein, phosphorylated GSK-3β, cyclin D1, and by increasing expression of p21 and p27 in human gastric cancer cell lines SGC-7901 and NCI-N87. Finally, DNEGFR induces apoptosis in these cells. Our results indicate that DNFGFR may provide promising treatment strategy for a subgroup of human gastric cancers that express EGFR.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liao
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Neng
authors.initials: N
authors.lastname: Zhang
authors.forename: Pujiang
authors.initials: P
authors.lastname: Dong
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000628:therapy*
chemical_list: D066246:ErbB Receptors