Differential expression of human nucleoside transporters in normal and tumor tissue.
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.
Pennycooke
M
M
Department of Biology, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3.
Chaudary
N
N
Shuralyova
I
I
Zhang
Y
Y
Coe
I R
IR
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D033703:Nucleoside Transport Proteins; D009705:Nucleosides / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D017931:DNA Primers; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033703:Nucleoside Transport Proteins; D009705:Nucleosides; C438649:SLC29A1 protein, human; C438654:SLC29A2 protein, human; C065171:cif nucleoside transporter