The aim of this study was to investigate the effect and mechanism of TGF-β in GC using GC cell line NOZ cells.In vitro cultured NOZ cell was randomly assigned into control, si-NC and TGF-β1 siRNA groups and were transfected with siRNA negative control (NC) or TGF-β1 siRNA followed by analysis of TGF-β1 expression by Real-time PCR, cell proliferation by MTT assay, cell apoptosis and cell invasion, as well as expression of proteins in epithelial-mesenchymal transition (EMT), p38, Smad2/3 and Smad4 phosphorylation by Western blot, Insulin-like growth factor-binding protein-2 (IGFBP-2) level by ELISA.
Frequent mutations were identified in tumor protein 53 (<i>TP53</i>) (14/27), SMAD family member 4 (<i>SMAD4</i>) (6/27), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (<i>PIK3CA</i>) (6/27), and Kirsten rat sarcoma (<i>KRAS</i>) (6/27); no significant differences were identified between EBDC and GBC tissues.
This study suggests that the DPC4 gene may play a limited role in gallbladder carcinoma; however, p53 gene mutation is more frequently found in gallbladder cancers.
Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in non-small cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss.