UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues
Nathan R Jones1, Philip Lazarus
1Department of Pharmacology, Pennsylvania State College of Medicine, Hershey, Pennsylvania (N.R.J.); and Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington (P.L.).
Abstract:
The UDP-glucuronosyltransferase (UGT) 2B subfamily of enzymes plays an important role in the metabolism of numerous endogenous and exogenous compounds, including various carcinogens present in tobacco smoke. The goal of the present study was to examine the levels of expression of individual UGT2B genes in various tissues that are targets for tobacco carcinogenesis. Using MT-ATP6 as the experimentally validated housekeeping gene, the highest extrahepatic expression of UGT2B genes was observed in human tonsil, with UGT2B expression levels similar to that observed in human liver. UGT2B17 exhibited high relative expression in most tissues examined, including lung, most tissues of the aerodigestive tract, and pancreas. UGT2B7 expression was highest in pancreas but low or undetectable in most other tissues examined. UGT2B10 expression was high in both tonsil and tongue. There was wide variability between individuals in the magnitude of expression in each tissue site, and there were strong correlations between UGT2B expression levels in different individuals within many of the tissue sites, suggesting coordinated regulation of UGT2B gene expression in extrahepatic tissues. In the liver, UGTs 2B4, 2B7, 2B10, and 2B15 were significantly correlated with each other (all r(2) > 0.70, P < 0.0001). In all examined tissues of the aerodigestive tract, UGTs 2B10, 2B11, and 2B17 exhibited a strong correlation with each other (all r(2) > 0.75, P < 0.05). UGTs 2B7 and 2B10 exhibited a strong inverse correlation in the pancreas (r(2) = -0.95, P < 0.01). These data suggest that specific UGT2B enzymes important in tobacco carcinogen metabolism are expressed and coordinately regulated in various target sites for tobacco-related cancers.
Insights
Specific UDP-glucuronosyltransferase (UGT) 2B enzymes, crucial for metabolizing tobacco carcinogens, are expressed and regulated in tissues targeted by tobacco-related cancers. This study mapped UGT2B gene expression across various human tissues.
Area of Science:
- Pharmacology
- Molecular Biology
- Cancer Research
Background:
- UDP-glucuronosyltransferase (UGT) 2B enzymes metabolize endogenous and exogenous compounds.
- These enzymes are critical in detoxifying carcinogens found in tobacco smoke.
- Understanding UGT2B expression in target tissues is vital for cancer research.
Purpose of the Study:
- To investigate the expression levels of individual UGT2B genes in human tissues susceptible to tobacco carcinogenesis.
- To identify specific UGT2B isoforms and their distribution in extrahepatic tissues relevant to tobacco exposure.
Main Methods:
- Quantitative analysis of UGT2B gene expression across various human tissues.
- Utilized MT-ATP6 as a validated housekeeping gene for normalization.
- Statistical analysis to assess correlations and variability in gene expression.
Main Results:
- Highest extrahepatic UGT2B expression observed in human tonsil, comparable to liver.
- UGT2B17 showed high expression in lung, aerodigestive tract, and pancreas.
- UGT2B7 expression highest in pancreas; UGT2B10 high in tonsil and tongue.
- Significant correlations indicated coordinated UGT2B regulation in extrahepatic tissues.
Conclusions:
- Specific UGT2B enzymes involved in tobacco carcinogen metabolism are expressed in key target tissues.
- Evidence suggests coordinated regulation of UGT2B gene expression in extrahepatic sites.
- Findings contribute to understanding individual susceptibility to tobacco-related cancers.
