Molecular identification and characterization of rat Abcc1 cDNA: existence of two splicing variants and species difference in drug-resistance profile.
The human ABCC1 gene, a member of the ATP-binding cassette transporter super-family, plays a critical role in conferring cancer cell resistance to chemotherapeutic drugs. In the present study, we have cloned the full-length cDNA of rat Abcc1 and evaluated its significance in drug resistance. Analysis using the currently available genome database revealed that the rat Abcc1 gene is located on rat chromosome 13 and consists of at least 30 exons. The rat Abcc1 cDNA cloned from the spleen was 4981-bp long, within which two additional splicing variants were discovered. The rat Abcc1 gene is expressed in a wide variety of organs, with the highest expression being observed in the spleen. Human embryonic kidney 293 cells were transfected with the rat Abcc1/pcDNA3.1 vector to stably express rat Abcc1. Overexpression of rat Abcc1 elicited high resistance to etoposide. In contrast to the hitherto known drug-resistance profile of human ABCC1, rat Abcc1 did not significantly confer cellular resistance to anthracyclins or Vinca alkaloids. Our results strongly suggest that there is a significant species difference between human ABCC1 and rat Abcc1 in their contribution to the drug-resistance profile.
Takayanagi
Shin-Ichiro
S
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Ishikawa
Toshihisa
T
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D018432:Drug Resistance, Multiple; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D051381:Rats; D016415:Sequence Alignment; D013045:Species Specificity; D014162:Transfection
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1