Analysis of gene expression profile in gastric cancer cells stimulated with Helicobacter pylori isogenic strains

Abstract

To understand the biological processes within host cells induced by VacA, isogenic strains of Helicobacter pylori (NCTC 11638 or 11638-˜vacA) were used to stimulate gastric cancer cells SGC7901, and differentially expressed genes in host cells were identified using cDNA microarray technology. More than 300 genes were found to alter their mRNA expression at different time points, among which 68 were related to the cytoskeleton, 87 were associated with cell cycle, cell death and proliferation, IL8 expression was also found to be up-regulated. Cells co-cultured with broth-culture supernatant (BCS) of NCTC 11638 showed more alteration in microtubule cytoskeleton morphology, as observed by laser scanning confocal microscopy, and a lower apoptosis rate, detected by flow cytometry, compared with those co-cultured with BCS of 11638-˜vacA. The supernatants of cells co-cultured with NCTC 11638 showed significantly higher IL8 expression than those co-cultured with 11638-˜vacA. It is concluded that VacA disrupts cytoskeletal architecture by influencing the expression of cytoskeleton-associated genes. VacA breaks the balance between cell proliferation and cell death by inducing the maladjustment of genes related to cell cycle. VacA is also able to induce the inflammatory response.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

“…Currently, there are more than 20 identified MMPs that can be categorized by substrate specificity. Despite the clinical significance of the pathogenetic impact of MMPs in human cancer, including BC, only a few studies of MMPs are available in the literature, and those mainly analyze protein expression [12]. …”

Remodeling the host environment: modulation of the gastric epithelium by the Helicobacter pylori vacuolating toxin (VacA)

“…VacA-mediated cytoskeletal alterations in both actin filaments and the microtubule system have been reported (Ashorn et al, 2000; Pai et al, 2000; Tabel et al, 2003; Yuan et al, 2004; Hennig et al, 2005; Wang et al, 2005). Studies emerging from a yeast two-hybrid screen suggested that, at least in this system, VacA interacted with an intermediate filament interacting protein (de Bernard et al, 2000).…”

“…Studies emerging from a yeast two-hybrid screen suggested that, at least in this system, VacA interacted with an intermediate filament interacting protein (de Bernard et al, 2000). Moreover, VacA may alter the expression of multiple cytoskeletal-related genes (Pai et al, 2000; Yuan et al, 2004; Wang et al, 2005), although the mechanisms underlying these cytoskeletal alterations have not been demonstrated.…”

Transcriptome Analysis: Towards a Comprehensive Understanding of Global Transcription Activity

“…In particular, many new virulence factors have been identified without having to revert to the laborious techniques of the past [22]. The true importance of transcriptomics and microarrays is probably best shown by the diverse range of areas in addition to pathogen transcriptomics to which microarrays are contributing significantly, including (among many others) operon identification [49], gene essentiality studies [50], genotyping [19], detection of virulent isolates [51], elucidation of the host response to infection [52], and the effect of virulent organisms on host cells [53]. Transcriptomics is used as an indication of cellular activity at the protein level.…”