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Vol 44(2010) N 2 p. 208-215;
E.S. Kropotova1, R.A. Tychko1, O.L. Zinovyeva1, A.F. Zyryanova1, S.L. Hankin2, V.L. Cherkes3, V.A. Aliev3, S.F. Beresten1, N.I. Oparina1, T.D. Mashkova1*

Downregulation of AKR1B10 Expression in Colorectal Cancer

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Medical Center of the Bank of Russia, Moscow, 117593 Russia
3Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia

*mashkova@eimb.ru
Received - 2009-07-23; Accepted - 2009-08-13

Colorectal cancer is one of the most common cancers in the world. Changes in AKR1B1 and AKR1B10 expression levels, whose diagnostic value was previously shown for several other cancer types, were studied in colorectal tumors. These genes encode aldose reductases, members of the aldo-keto reductase superfamily, which comprises enzymes capable to reduce a range of aromatic and aliphatic aldehydes and ketones. They are also involved in retinoid metabolism and carcinogenesis. AKR1B1 and AKR1B10 mRNA levels were compared in paired specimens of normal and colorectal tumor tissues using RT--PCR and quantitative real-time PCR. For the first time, the downregulation of these genes was demonstrated in colorectal carcinoma. AKR1B10 expression was decreased in most tumor specimens (88%, 65/74) even at the early stages, and in more than 60% of cases mRNA levels were decreased more than 10-fold. AKR1B1 mRNA levels were decreased in 10% of specimens. Therefore, these two structurally similar genes show quite different mRNA expression patterns in colorectal cancer, suggestive of their different functional roles in the intestine. Significant downregulation of AKR1B10 expression can be considered a potential diagnostic marker of colorectal cancer.

aldo-keto reductase family 1, B1 and B10 aldose reductases, colorectal cancer, gene expression, RT--PCR, real time PCR, tumor markers



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