Skip to main content
SpringerLink
Log in

Downregulation of AKR1B10 expression in colorectal cancer

  • Genomics. Transcriptomics
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AKR:

aldo-keto redudase

AKR1B1 and AKR1B10:

aldose redudases B1 and B10

CRC:

colorectal cancer

PCR:

polymerase chain reaction

RT-PCR:

reverse transcription with the subsequent PCR

PCR-RT:

PCR in real time

References

  1. Hyndman D., Bauman D.R., Heredia V.V., Penning T.M. 2003. The aldo-keto reductase superfamily homepage. Chem. Biol. Interact. 143/144, 621–631.

    Article  Google Scholar 

  2. Jin Y., Penning T.M. 2007. Aldo-keto reductases and bioactivation/detoxication. Annu. Rev. Pharmacol. Toxicol. 47, 263–292.

    Article  CAS  PubMed  Google Scholar 

  3. Cao D., Fan S.T., Chung S.S. 1998. Identification and characterization of a novel human aldose reductase-like gene. J. Biol. Chem. 273, 11429–11435.

    Article  CAS  PubMed  Google Scholar 

  4. Yabe-Nishimura C. 1998. Aldose reductase in glucose toxicity: A potential target for the prevention of diabetic complications. Pharmacol. Rev. 50, 21–33.

    CAS  PubMed  Google Scholar 

  5. Ko B., Ruepp B., Bohren K.M., Gabbay K.H., Chung S.S. 1997. Identification and characterization of multiple osmotic response sequences in the human aldose reductase gene. J. Biol. Chem. 272, 16431–16437.

    Article  CAS  PubMed  Google Scholar 

  6. Liu Z., Zhong L., Krishack P.A., Robbins S., Cao J.X., Zhao Yu., Chung S., Cao D. 2009. Structure and promoter characterization of aldo-keto reductase family 1 B10 gene. Gene. 437, 39–44.

    Article  CAS  PubMed  Google Scholar 

  7. Crosas B., Hyndman D.J., Gallego O., Martras S., Parés X., Flynn T.G., Farrés J. 2003. Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: Consequences for retinoid metabolism. Biochem. J. 373, 973–979.

    Article  CAS  PubMed  Google Scholar 

  8. Gallego O., Belyaeva O.V., Porté S., Ruiz F.X., Stetsenko A.V., Shabrova E.V., Kostereva N.V., Farrés J., Parés X., Kedishvili N.Y. 2006. Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases, and aldo-keto reductases with retinoids. Biochem. J. 399, 101–109.

    Article  CAS  PubMed  Google Scholar 

  9. Grimshaw C.E., Mathur E.J. 1989. Immunoquantitation of aldose reductase in human tissues. Anal. Biochem. 176, 66–71.

    Article  CAS  PubMed  Google Scholar 

  10. Hyndman D.J., Flynn T.G. 1998. Sequence and expression levels in human tissues of a new member of the aldo-keto reductase family. Biochim. Biophys. Acta. 1399, 198–202.

    CAS  PubMed  Google Scholar 

  11. Penning T.M., Drury J.E. 2007. Human aldo-keto reductases: Functions, gene regulation, and single nucleotide polymorphisms. Arch. Biochem. Biophys. 464, 241–250.

    Article  CAS  PubMed  Google Scholar 

  12. Fukumoto S., Yamauchi N., Moriguchi H., Hippo Y., Watanabe A., Shibahara J., Taniguchi H., Ishikawa S., Ito H., Yamamoto S., Iwanari H., Hironaka M., Ishikawa Y., Niki T., Sohara Y., Kodama T., Nishimura M., Fukayama M., Dosaka-Akita H., Aburatani H. 2005. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers’ nonsmall cell lung carcinomas. Clin. Cancer Res. 11, 1776–1785.

    Article  CAS  PubMed  Google Scholar 

  13. Penning T.M. 2005. AKR1B10: A new diagnostic marker of non-small cell lung carcinoma in smokers. Clin. Cancer Res. 11, 1687–1690.

    Article  CAS  PubMed  Google Scholar 

  14. Ruiz F.X, Gallego O., Ardevol A., Moro A., Dominguez M., Alvarez S., Alvarez R., de Lera A.R., Rovira C., Fita I., Parés X., Farrés J. 2009. Aldo-keto reductases from the AKR1B subfamily: Retinoid specificity and control of cellular retinoic acid levels. Chem. Biol. Interact. 178, 171–177.

    Article  CAS  PubMed  Google Scholar 

  15. Mashkova T.D., Oparina N.I., Zinovyeva O.L., Kropotova E.S., Dubovaya V.I., Poltaraus A.V., Fridman M.V., Kopantsev E.P., Vinogradova T.M., Zinovyeva M.V., Laktionov K.K., Kasymova O.T., Zborovskaya I.V., Sverdlov E.D., Kisselev L.L. 2006. Transcription of TIMP3, DAPK1, and AKR1V10 in squamous-cell lung cancer. Mol. Biol. 40, 945–951.

    Article  CAS  Google Scholar 

  16. Nagaraj N.S., Beckers S., Mensah J.K., Waigel S., Vigneswaran N., Zacharias W. 2006. Cigarette smoke condensate induces cytochromes P450 and aldo-keto reductases in oral cancer cells. Toxicol. Lett. 165, 182–194.

    Article  CAS  PubMed  Google Scholar 

  17. Scuric Z., Stain S.C., Anderson W.F., Hwang J.J. 1998. New member of aldose reductase family proteins over-expressed in human hepatocellular carcinoma. Hepatology. 27, 943–950.

    Article  CAS  PubMed  Google Scholar 

  18. Lee K.W., Ko B.C., Jiang Z., Cao D., Chung S.S. 2001. Overexpression of aldose reductase in liver cancers may contribute to drug resistance. Anticancer Drugs. 12, 129–132.

    Article  CAS  PubMed  Google Scholar 

  19. Yoshitake H., Takahashi M., Ishikawa H., Nojima M., Iwanari H., Watanabe A., Aburatani H., Yoshida K., Ishi K., Takamori K., Ogawa H., Hamakubo T., Kodama T., Araki Y. 2007. Aldo-keto reductase family 1, member B10 in uterine carcinomas: A potential risk factor of recurrence after surgical therapy in cervical cancer. Int. J. Gynecol. Cancer. 17, 1300–1306.

    Article  CAS  PubMed  Google Scholar 

  20. Hyndman D., Flynn T.G. 1999. The aldo-keto reductases and their role in cancer. Adv. Exp. Med. Biol. 463, 427–434.

    CAS  PubMed  Google Scholar 

  21. Jin J., Krishack P.A., Cao D. 2006. Role of aldo-keto reductases in development of prostate and breast cancer. Front Biosci. 11, 2767–2773.

    Article  CAS  PubMed  Google Scholar 

  22. Saraswat M., Mrudula T., Kumar P.U., Suneetha A., Rao T.S., Srinivasulu M., Reddy B. 2006. Overexpression of aldose reductase in human cancer tissues. Med. Sci. Monit. 12, CR525–CR529.

    CAS  PubMed  Google Scholar 

  23. Jemal A., Siegel R., Ward E., Murray T., Xu J., Smigal C., Thun M.J. 2006. Cancer statistics. CA Cancer J. Clin. 56, 36–30.

    Article  Google Scholar 

  24. Manzeniuk O.Y., Malakho S.G., Pekhov V.M., Kosorukova I.S., Poltaraus A.V. 2006. Characterization of Russian universal kits for real-time PCR: Application to molecular oncodiagnosis. Mol. Biol. 40, 305–311.

    Article  CAS  Google Scholar 

  25. Hackenberg M., Previti C., Luque-Escamilla P.L., Carpena P., Martinez-Aroza J., Oliver J.L. 2006. CpG-cluster: A distance-based algorithm for CpG-island detection. BMC Bioinform. 7, 446.

    Article  Google Scholar 

  26. Lefrancois-Martinez A.M., Bertherat J., Val P., Tournaire C., Gallo-Payet N., Hyndman D., Veyssiere G., Bertagna X., Jean C., Martinez A. 2004. Decreased expression of cyclic adenosine monophosphate-regulated aldose reductase (AKR1B1) is associated with malignancy in human sporadic adrenocortical tumors. J. Clin. Endocrinol. Metab. 89, 3010–3019.

    Article  CAS  PubMed  Google Scholar 

  27. Camps J., Grade M., Nguyen O.T., Hormann P., Becker S., Hummon A.B., Rodriguez V., Chandrasekharappa S., Chen Y., Difilippantonio M.J., Becker H., Ghadimi B.M., Ried T. 2008. Chromosomal breakpoints in primary colon cancer at sites of structural variants in the genome. Cancer Res. 68, 1284–1295.

    Article  CAS  PubMed  Google Scholar 

  28. von Lintig J., Vogt K. 2000. Filling the gap in vitamin A research: Molecular identification of an enzyme cleaving beta-carotene to retinal. J. Biol. Chem. 275, 11915–11920.

    Article  Google Scholar 

  29. Martin H.J., Maser E. 2009. Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes. Chem. Biol. Interact. 178, 145–150.

    Article  CAS  PubMed  Google Scholar 

  30. Ames B.N. 1983. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science. 221, 1256–1264.

    Article  CAS  PubMed  Google Scholar 

  31. Homann N., Tillonen J., Salaspuro M. 2000. Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency. Int. J. Cancer. 86, 169–173.

    Article  CAS  PubMed  Google Scholar 

  32. Zu X., Yan R., Robbins S., Krishack P.A., Liao D.F., Cao D. 2007. Reduced 293T cell susceptibility to acrolein due to aldose reductase-like-1 protein expression. Toxicol. Sci. 97, 562–528.

    Article  CAS  PubMed  Google Scholar 

  33. Yan R., Zu X., Ma J., Liu Z., Adeyanju M., Cao D. 2007. Aldo-keto reductase family 1B10 gene silencing results in growth inhibition of colorectal cancer cells: Implication for cancer intervention. Int. J. Cancer. 121, 2301–2306.

    Article  CAS  PubMed  Google Scholar 

  34. Kurtz A.J., Lloyd R.S. 2003. 1,N2-deoxyguanosine adducts of acrolein, crotonaldehyde, and trans-4-hydroxynonenal cross-link to peptides via Schiff base linkage. J. Biol. Chem. 278, 5970–5976.

    Article  CAS  PubMed  Google Scholar 

  35. Hashimoto M., Sibata T., Wasada H., Toyokuni S., Uchida K. 2003. Structural basis of protein-bound endogenous aldehydes: Chemical and immunochemical characterizations of configurational isomers of a 4-hydroxy-2-nonenal-histidine adduct. J. Biol. Chem. 278, 5044–5051.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    E. S. Kropotova, R. A. Tychko, O. L. Zinov’eva, A. F. Zyryanova, S. F. Beresten, N. Yu. Oparina & T. D. Mashkova

  2. Medical Center of the Central Bank of the Russian Federation, Moscow, 117593, Russia

    S. L. Khankin

  3. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    V. L. Cherkes & V. A. Aliev

Authors
  1. E. S. Kropotova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. A. Tychko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. L. Zinov’eva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. F. Zyryanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. L. Khankin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. L. Cherkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. A. Aliev
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. F. Beresten
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. Yu. Oparina
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T. D. Mashkova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. D. Mashkova.

Additional information

Original Russian Text © E.S. Kropotova, R.A. Tychko, O.L. Zinov’eva, A.F. Zyryanova, S.L. Khankin, V.L. Cherkes, V.A. Aliev, S.F. Beresten, N.Yu. Oparina, T.D. Mashkova, 2010, published in Molekulyarnaya Biologiya, 2010, Vol. 44, No. 2, pp. 243–250.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kropotova, E.S., Tychko, R.A., Zinov’eva, O.L. et al. Downregulation of AKR1B10 expression in colorectal cancer. Mol Biol 44, 216–222 (2010). https://doi.org/10.1134/S0026893310020056

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893310020056

Key words

Search

Navigation