Anti-FABP6 monoclonal antibody, clone 5B5

Background: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. Methods: In order to provide better understanding of the molecular biology of ccRCC and to identify potential diagnostic/prognostic biomarker and therapeutic targets, we utilized a microarray to profile mRNA expression of corresponding normal and malignant renal tissues. Real-time PCR, Western Blot and immunohistochemistry were applied to study the expression of candidate biomarkers. ccRCC cell lines were treated with sertraline to inhibit the dopamine transporter SLC6A3. Results: Differential expression of fourteen mRNAs, yet not studied in ccRCC in depth, was confirmed using qPCR (upregulation: SLC6A3, NPTX2, TNFAIP6, NDUFA4L2, ENPP3, FABP6, SPINK13; downregulation: FXYD4, SLC12A1, KNG1, NPHS2, SLC13A3, GCGR, PLG). Up-/downregulation was also confirmed for FXYD4, KNG1, NPTX2 and SLC12A1 by Western Blot on the protein level. In contrast to the mRNA expression, protein expression of the dopamine transporter SLC6A3 was lower in ccRCC compared to normal renal tissue. Immunohistochemistry indicated that this decrease was due to higher concentrations of SLC6A3 in the proximal tubules. Immunohistochemical analyses further demonstrated that high SLC6A3 expression in ccRCC tissue was correlated with a shorter period of recurrence-free survival following surgery. Treatment of ccRCC cells with the SLC6A3 inhibitor sertraline induced dose-dependent cell-death. Conclusion: Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted.

ScopeThe molecular mechanisms underlying the cholesterol-lowering properties of oats are only partly known. To study possible pathways involved, we investigated gene expressions in the liver and small intestine of mice fed oats. Method and resultsCholesterol and bile acids were analyzed in plasma and feces from LDL-receptor deficient (LDLr-/-) mice fed Western diet with wholegrain oats. A transcriptome analysis of mRNA from liver and jejunum was performed together with quantitative RT-PCR. Oat-fed mice had lower levels of plasma lipids and increased levels of bile acids and cholesterol in feces compared with controls. Two hundred thirty nine genes in jejunum and 25 genes in liver were differentially expressed (FDR corrected p < 0.05). The most affected biological process in jejunum was lipid biosynthesis and regulation. The apical sodium-dependent bile acid transporter (ASBT, Slc10a) and the intracellular bile acid binding protein (Fabp6) were both upregulated, whereas small heterodimer partner-1 (Shp-1) and apolipoprotein CII (Apoc2) were downregulated. ConclusionsWhole oats attenuated responses typically induced by high-fat diet. Increased expression of genes for intestinal bile acid uptake following oat consumption suggests retention in the gut lumen rather than decreased uptake capacity as cause for the increased bile acid excretion and the concomitant reduction of plasma cholesterol.