Aldehyde dehydrogenase 1B1 (ALDH1B1) is a potential biomarker for human colon cancer - PubMed (original) (raw)

Aldehyde dehydrogenase 1B1 (ALDH1B1) is a potential biomarker for human colon cancer

Ying Chen et al. Biochem Biophys Res Commun. 2011.

Abstract

Aldehyde dehydrogenases (ALDHs) belong to a superfamily of NAD(P)+-dependent enzymes, which catalyze the oxidation of endogenous and exogenous aldehydes to their corresponding acids. Increased expression and/or activity of ALDHs, particularly ALDH1A1, have been reported to occur in human cancers. It is proposed that the metabolic function of ALDH1A1 confers the "stemness" properties to normal and cancer stem cells. Nevertheless, the identity of ALDH isozymes that contribute to the enhanced ALDH activity in specific types of human cancers remains to be elucidated. ALDH1B1 is a mitochondrial ALDH that metabolizes a wide range of aldehyde substrates including acetaldehyde and products of lipid peroxidation (LPO). In this study, we immunohistochemically examined the expression profile of ALDH1A1 and ALDH1B1 in human adenocarcinomas of colon (N=40), lung (N=30), breast (N=33) and ovary (N=33) using an NIH tissue array. The immunohistochemical expression of ALDH1A1 or ALDH1B1 in tumor tissues was scored by their intensity (scale=1-3) and extensiveness (% of total cancer cells). Herein we report a 5.6-fold higher expression score for ALDH1B1 in cancerous tissues than that for ALDH1A1. Remarkably, 39 out of 40 colonic cancer specimens were positive for ALDH1B1 with a staining intensity of 2.8±0.5. Our study demonstrates that ALDH1B1 is more profoundly expressed in the adenocarcinomas examined in this study relative to ALDH1A1 and that ALDH1B1 is dramatically upregulated in human colonic adenocarcinoma, making it a potential biomarker for human colon cancer.

Copyright © 2011 Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. Distribution of ALDH1A1 and ALDH1B1 in normal human tissues by IHC

Positive staining (brown) displayed a diffuse cytoplasmic pattern for ALDH1A1 (A), but a cytoplasmic punctate pattern for ALDH1B1 (B). Hepatocytes were strongly stained for both proteins. In the colon, cells at the crypt bottom were positively stained with both ALDH1A1 and ALDH1B1 (arrows), whereas the immunopositivity of ALDH1A1 was also noted in partially differentiated cells at higher crypt levels (arrowheads). The bronchiole epithelium and Clara cells in the lung showed immunopositivity of ALDH1A1 and to a lesser extend of ALDH1B1. In the breast, IHC-signal of ALDH1A1 was barely notable and observed only in luminal epithelial cells (arrows); in contrast, the acinar and ductal lining columnar cells and the basal cells beneath them were all positively stained for ALDH1B1. In the ovary, the surface simple cuboidal cells (arrows) stained negatively for ALDH1A1, but quite intensely for ALDH1B1. Representative images are presented at two magnifications, with the squared field in the top panel (400×) enlarged in the bottom panel (1000×).

Figure 2

Figure 2. Expression of ALDH1A1 and ALDH1B1 in human adenocarcinoma by IHC

(A) Cancer specimens stained with anti-ALDH1A1 showed positive cystoplasmic staining (brown) in ~20% cancer cells (solid arrows) and negative staining in neighboring cancer cells (open arrows). (B) Cancer specimens stained with anti-ALDH1B1 showed strong positive punctate staining (brown) in almost all cancer cells. Representative images are presented at two magnifications, with the squared field in the top panel (200×) enlarged in the bottom panel (1000×).

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