Downregulation of AKR1B10 gene expression in colorectal cancer
Abstract
Colorectal cancer is one of the most common cancers in the world.
In our work changes of AKR1B1 and AKR1B10 gene expression levels in colorectal tumors were studied. Their potential diagnostic value was previously shown for several other cancer types.
These genes encode aldoso reductases, which belong to the aldo-keto reductases superfamily consisting of enzymes capable to reduce numerous aromatic and aliphatic aldehydes and ketones.
They are also involved into retinoid metabolism and cancerogenesis.
We have carried out comparative analysis of mRNA levels of AKR1B1 and AKR1B10 genes in paired samples of normal and colorectal tumor tissues using RT-PCR and quantitative PCR. We have shown for the first time the decrease of activity of these genes in colorectal carcinomas.
Significant reduction of AKR1B10 mRNA level was detected in the most of tumor samples (88%, 65/74) even at the early stages of malignancy, and in more than 60% of cases this downregulation was much higher than 10 folds. The decrease of AKR1B1 mRNA level was shown in 10% of tumors only. Therefore, we have detected quite different mRNA expression patterns in colorectal cancer for these two structurally similar genes.
These data could indicate different functional roles of these two genes in colorectum. The significant decrease of AKR1B10 mRNA in most samples of colorectal cancer could be considered as potential diagnostic marker of this type of cancer.