Anti-SLC6A3 monoclonal antibody, clone iEBU-MPPQ

Purpose: Renal cell carcinoma (RCC) is derived from a tissue with a remarkable capacity for vectorial transport. We therefore performed an unbiased exploration of transporter proteins in normal kidney and kidney cancer to discover novel clinical targets. Experimental Design: Using The Cancer Genome Atlas (TCGA) database, we investigated differences in membrane transporter expression in clear cell RCC (ccRCC) and normal kidney. We identified the dopamine transporter SLC6A3 as a specific biomarker for ccRCC. To investigate the functionality of SLC6A3, we used a [H-3]-dopamine uptake assay on ccRCC cells. We further explored the effect of hypoxia-inducible factor (HIF) proteins on SLC6A3 expression by introducing siRNA in ccRCC cells and by hypoxic treatment of nonmalignant cells. Results: We show that ccRCC expresses very high transcript levels of SLC6A3 in contrast to normal kidney tissue and other tumor types, which do not express appreciable levels of this transporter. Importantly, we demonstrate that the elevated expression of SLC6A3 in ccRCC cells is associated with specific uptake of dopamine. By targeting the expression of HIF-1 alpha and HIF-2 alpha, we could show that SLC6A3 expression is primarily influenced by HIF-2 alpha and that hypoxia can induce SLC6A3 expression in normal renal cells. Conclusions: We conclude that the dopamine transporter SLC6A3 constitutes a novel biomarker that is highly specific for ccRCC. We further postulate that the protein can be exploited for diagnostic or therapeutic purposes for detection or treatment of ccRCC. (C) 2016 AACR.

Drug addiction is a complex neuropsychiatric disorder involving the environmental and genetic factors. Genetic and physiological evidences suggest that the dopaminergic system may play an important role in cocaine abuse and dependence. Several association studies have focused on dopaminergic genes. We genotyped the Int8 and 3'UTR variable number of tandem repeats of the dopamine transporter gene (DAT1/SLC6A3), the TaqIA (rs1800497) and TaqIB (rs1079597) SNP polymorphisms within the dopamine receptor D2 gene and the 19-bp insertion/deletion and c.444G > A (rs1108580) polymorphisms of the dopamine beta-hydroxylase gene (DBH) in a Spanish sample of 169 patients with cocaine addiction and 169 sex-matched controls. The case-control study showed a nominal overrepresentation of the 5R/5R genotype of the Int8 variable number of tandem repeats within DAT1 in cocaine abusers (P = 0.016). However, no significant associations were detected when DAT1 haplotype frequencies or polymorphisms within the other dopaminergic genes were considered. Sample size is limited and further studies should be performed in a larger cohort. Psychiatr Genet 20:317-320 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.