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Differential expression of human nucleoside transporters in normal and tumor tissue
M Pennycooke1, N Chaudary, I Shuralyova
1Department of Biology, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3.
Abstract:
Responses to nucleoside analog drugs used in the treatment of cancers and viral infections can vary considerably between individuals. Genetic variability between individuals in their ability to transport drugs may be a contributory factor. Nucleoside transporters (NTs) move nucleosides and analog drugs across cell membranes. Four human NTs have been cloned: hENT1, hENT2, hCNT1, and hCNT2. Human NT expression profiles are not well defined; therefore, we undertook a comprehensive quantitative analysis of the differential expression of NTs within normal and tumor tissue. Results show tissue specific expression of the different NTs in normal tissue while matched normal/tumor tissue cDNA array data show considerable variability in all NT expression profiles from different individuals, in particular decreased expression in tumor tissue. Decreased NT expression in tumor tissue may contribute to reduced drug uptake and the development of resistance. These data suggest that nucleoside analog drug therapies may be optimized by determining individual NT expression profiles.
Insights
Individual differences in nucleoside transporter (NT) expression impact cancer and viral drug efficacy. This study quantifies NT expression in normal and tumor tissues, revealing variability that may explain drug resistance and optimize therapies.
Area of Science:
- Pharmacogenomics
- Molecular Biology
- Cancer Research
Background:
- Individual responses to nucleoside analog drugs vary due to genetic factors influencing drug transport.
- Nucleoside transporters (NTs) facilitate the cellular uptake of nucleosides and analog drugs.
- Four human NTs (hENT1, hENT2, hCNT1, hCNT2) are known, but their expression profiles are not well-defined.
Purpose of the Study:
- To perform a comprehensive quantitative analysis of differential nucleoside transporter (NT) expression in normal and tumor tissues.
- To investigate the variability of NT expression among individuals and between normal and tumor tissues.
Main Methods:
- Quantitative analysis of differential NT expression.
- Utilized matched normal/tumor tissue cDNA array data.
Main Results:
- Demonstrated tissue-specific expression patterns for different NTs in normal tissues.
- Observed significant inter-individual variability in all NT expression profiles.
- Noted a particular decrease in NT expression within tumor tissues compared to matched normal tissues.
Conclusions:
- Decreased NT expression in tumors may lead to reduced drug uptake and contribute to drug resistance.
- Determining individual NT expression profiles could optimize nucleoside analog drug therapies.
- Highlights the importance of pharmacogenomic profiling for personalized cancer and antiviral treatments.