Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

Abstract

PURPOSE:

Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC.

EXPERIMENTAL DESIGN:

Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis.

RESULTS:

Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC.

CONCLUSION:

AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.

• Authors: Shin-ichi Fukumoto, Naoko Yamauchi, Hisashi Moriguchi, Yoshitaka Hippo, Akira Watanabe, Junji Shibahara, Hirokazu Taniguchi, Shumpei Ishikawa, Hirotaka Ito, Shogo Yamamoto, Hiroko Iwanari, Mitsugu Hironaka, Yuichi Ishikawa, Toshiro Niki, Yasunori Sohara, Tatsuhiko Kodama, Masaharu Nishimura, Masashi Fukayama, Hirotoshi Dosaka-Akita, Hiroyuki Aburatani
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 5 Pg. 1776-85 (Mar 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15755999 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Biomarkers, Tumor
• AKR1B10 protein, human
• Aldo-Keto Reductases
• Aldehyde Reductase

Topics

• Aldehyde Reductase (biosynthesis, genetics)
• Aldo-Keto Reductases
• Antibodies, Monoclonal
• Biomarkers, Tumor (biosynthesis, genetics)
• Carcinoma, Non-Small-Cell Lung (etiology, genetics)
• Case-Control Studies
• Gene Expression Profiling
• Humans
• Immunohistochemistry
• Lung Neoplasms (etiology, genetics, pathology)
• Oligonucleotide Array Sequence Analysis
• Smoking (adverse effects)
• Tumor Cells, Cultured
• Up-Regulation