PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
Blotting, Western ; Caffeic Acids ; Cell Line, Tumor ; Cell Proliferation ; DNA, Bacterial/analysis/genetics ; DNA-Binding Proteins/*metabolism ; Epithelial Cells/*metabolism ; Gastric Mucosa/*metabolism/pathology ; Gastritis/pathology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/metabolism/pathology/physiopathology ; Helicobacter pylori/pathogenicity/physiology ; Humans ; NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism ; Peptide Fragments ; Phenylethyl Alcohol/analogs & derivatives ; Proto-Oncogene Proteins c-jun ; Repressor Proteins ; Transcription Factor AP-1/*biosynthesis ; Transcription Factors/*metabolism ; beta Catenin/*metabolism

Purpose: Breast cancer is mainly diagnosed using core needle biopsy (CNB), although other biopsy methods, including vacuum-assisted biopsy (VAB), may also be used. We compared differences in clinical characteristics and prognoses of patients with breast cancer according to biopsy methods used for diagnosis. Methods: A total of 98,457 patients who underwent various biopsy methods (CNB, fine-needle aspiration [FNA], VAB, and excisional biopsy) for diagnosing breast cancer were recruited. Using CNB as a reference, related clinicopathological factors and prognostic differences between biopsy methods were analyzed retrospectively using large-scale data from the Korean Breast Cancer Society Registration System. The associations between biopsy methods and clinicopathological factors were compared using multinomial logistic regression analysis, and the prognoses of patients undergoing the different biopsy methods, as breast cancer-specific survival (BCSS) and overall survival (OS), were compared using the Kaplan-Meier method and Cox proportional hazard model. Results: Univariate and multivariate analyses showed that unlike FNA, both VAB and excisional biopsy were significantly associated with tumor size, palpability, tumor stage, and histologic grade as relatively good prognostic factors compared to CNB. In particular, VAB showed lower odds ratios for these factors than excisional biopsy. In the univariate analysis, the prognosis of patients undergoing VAB was better than that of those undergoing CNB with respect to BCSS (hazard ratio [HR], 0.188, p < 0.001) and OS (HR, 0.359; p < 0.001). However, in the multivariate analysis, there were no significant prognostic differences from CNB in both BCSS and OS; differences were only evident for FNA. Conclusion In this study, we showed that the characteristics of breast cancer differed according to various biopsy methods. Although VAB is not a standard method for breast cancer diagnosis, it showed no prognostic differences to CNB.