Expression of genes involved in retinoic acid biosynthesis in human gastric cancer

All-trans-retinoic acid (ATRA) is the main biologically active metabolite of retinol (vitamin A) that is required for the regulation of processes such as embryogenesis, tissue differentiation, proliferation, and others. Multiple alcohol, retinol, and retinaldehyde dehydrogenases (ADHs, RDHs, and RALDHs), as well as aldo-keto reductases (AKRs) catalyze the biosynthesis of retinoic acid in humans. For many normal and neoplastic tissues, the key ATRA-synthesizing enzymes remain unknown. We identified ATRA-generating genes that are expressed in normal and malignant gastric tissues using the transcriptomic database analysis. Quantitative changes in the expression levels of these genes in gastric cancer were determined by semi-quantitative RT-PCR and real-time PCR. Significant decreases in the mRNA levels of genes that encode the enzymes that catalyze the reversible oxidation/reduction of retinol and retinaldehyde (ADH4, ADH1B, ADH1C, RDHL, AKR1B10, AKR1B1, and RDH12), as well as the oxidation of retinaldehyde (RALDH1) were revealed in most tumor samples. A sharp reduction in the expression levels of genes encoding the key enzymes that convert retinol and retinaldehyde to retinoic acid could lead to a significant decrease in the content of ATRA, the transcriptional regulator of many genes, which can in turn lead to the dysregulation of cell proliferation/differentiation and initiate the development of cancer.