Expression of the Aldo-Ketoreductases AKR1B1 and AKR1B10 in Human Cancers

Brian Laffin,J Mark Petrash

doi:10.3389/fphar.2012.00104

Abstract

The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-ketoreductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com). Using this database, we found that expression of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

Highlights

Cancer is the second leading cause of death in the U.S behind heart disease, and the American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011
Since AKR1B1 has been shown to be involved in many cellular processes relevant to cancer such as EMT (Zablocki et al, 2011), inflammation (Yadav et al, 2007, 2009, 2011), and angiogenesis (Tammali et al, 2011b,c), and AKR1B10 is known to have relevance to human cancers, we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com)
To determine whether the aldo-ketoreductases AKR1B1 and AKR1B10 were differentially expressed between cancerous and normal tissues, we broadly examined microarray data from patient samples contained within the Oncomine database

Summary

Introduction

Cancer is the second leading cause of death in the U.S behind heart disease, and the American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011. Identification of new therapeutic targets and development of novel cancer therapies is still a pressing need. As well-characterized inhibitors for these enzymes are already in use or development, they would seem to be attractive targets for cancer therapeutic development. These studies have been conducted largely in model systems, and there is very little known about the involvement of AKR1B10 in cancer outside of the lungs and liver, and while AKR1B1 expression has been reported to be elevated in human cancers, this study was limited by a small number of available patient samples (Saraswat et al, 2006). Since AKR1B1 has been shown to be involved in many cellular processes relevant to cancer such as EMT (Zablocki et al, 2011), inflammation (Yadav et al., 2007, 2009, 2011), and angiogenesis (Tammali et al, 2011b,c), and AKR1B10 is known to have relevance to human cancers, we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com)

Methods

Results

Conclusion