ADH IB expression, but not ADH III, is decreased in human lung cancer

PLoS One. 2012;7(12):e52995. doi: 10.1371/journal.pone.0052995. Epub 2012 Dec 28.

Abstract

Endogenous S-nitrosothiols, including S-nitrosoglutathione (GSNO), mediate nitric oxide (NO)-based signaling, inflammatory responses, and smooth muscle function. Reduced GSNO levels have been implicated in several respiratory diseases, and inhibition of GSNO reductase, (GSNOR) the primary enzyme that metabolizes GSNO, represents a novel approach to treating inflammatory lung diseases. Recently, an association between decreased GSNOR expression and human lung cancer risk was proposed in part based on immunohistochemical staining using a polyclonal GSNOR antibody. GSNOR is an isozyme of the alcohol dehydrogenase (ADH) family, and we demonstrate that the antibody used in those studies cross reacts substantially with other ADH proteins and may not be an appropriate reagent. We evaluated human lung cancer tissue arrays using monoclonal antibodies highly specific for human GSNOR with minimal cross reactivity to other ADH proteins. We verified the presence of GSNOR in ≥85% of specimens examined, and extensive analysis of these samples demonstrated no difference in GSNOR protein expression between cancerous and normal lung tissues. Additionally, GSNOR and other ADH mRNA levels were evaluated quantitatively in lung cancer cDNA arrays by qPCR. Consistent with our immunohistochemical findings, GSNOR mRNA levels were not changed in lung cancer tissues, however the expression levels of other ADH genes were decreased. ADH IB mRNA levels were reduced (>10-fold) in 65% of the lung cancer cDNA specimens. We conclude that the previously reported results showed an incorrect association of GSNOR and human lung cancer risk, and a decrease in ADH IB, rather than GSNOR, correlates with human lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Alcohol Dehydrogenase / genetics*
  • Alcohol Dehydrogenase / metabolism
  • Aldehyde Oxidoreductases / genetics
  • Aldehyde Oxidoreductases / metabolism
  • Antibodies, Monoclonal / metabolism
  • Case-Control Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • RNA, Messenger / analysis
  • S-Nitrosoglutathione / metabolism

Substances

  • Antibodies, Monoclonal
  • RNA, Messenger
  • S-Nitrosoglutathione
  • ADH1B protein, human
  • ADH1C protein, human
  • Alcohol Dehydrogenase
  • Aldehyde Oxidoreductases
  • formaldehyde dehydrogenase, glutathione-independent

Grants and funding

N30 Pharmaceuticals, Inc is a privately held company. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.