Cyclin D1 G870A gene polymorphism and risk of leukemia and hepatocellular carcinoma: a meta-analysis.

Cyclin D1 (CCND1) is a key protein involved in cell-cycle regulation, and the CCND1 G870A polymorphism is associated with many types of malignancy. Studies examining the associations between this G870A polymorphism and susceptibility to leukemia and hepatocellular carcinoma (HCC) have shown inconsistent results. Therefore, we conducted a meta-analysis to clarify these associations. A search of the PubMed database yielded 7 relevant articles: 3 pertaining to leukemia and 4 to HCC. The odds ratios (ORs) from individual studies were pooled using a fixed or random-effect model. A significant association was observed between the CCND1 G870A variant and leukemia under the allele contrast model [P = 0.003, OR = 1.49, 95% confidence interval (CI) = 1.15-1.95], the homozygote contrast model (P = 0.003, OR = 2.30, 95%CI = 1.34-3.96), and the recessive model (P = 0.002, OR = 2.03, 95%CI = 1.29-3.21). A significant association was observed between this variant and HCC under the recessive model (P = 0.0006, OR = 1.62, 95%CI = 1.23-2.14), the dominant model (P = 0.002, OR = 1.59, 95%CI = 1.19-2.14), the homozygote contrast model (P < 0.0001, OR = 2.06, 95%CI = 1.45-2.94), and the allele contrast model (P < 0.0001, OR = 1.43, 95%CI = 1.20-1.69). Our findings suggest that heritable CCND1 status may influence the risk of developing leukemia and HCC, and that more attention should be given to carriers of these susceptibility genes.

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells.

The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-alpha) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell microporous filters and treated with TNF-alpha (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-alpha treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-alpha decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-alpha did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-alpha increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-á) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-á (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-á treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-á decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-á did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-á increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.