Endoscopy 2004; 36 - 1
DOI: 10.1055/s-2004-824983

The Arginine Transporter ATB(0,+) is Upregulated in Colorectal Cancer

N Gupta 1, S Miyauchi 1, H Hu 1, A Herdman 1, R Podolsky 1, PM Martin 1, S Mager 1, RG Martindale 1, V Ganapathy 1
  • 1Departments of Surgery, Biochemistry and Molecular Biology, Pathology and Biostatistics, Medical College of Georgia, Augusta, Georgia, USA and the Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Introduction: Excess production of nitric oxide (NO) from arginine by the enzyme iNOS plays a crucial role in colorectal cancer. Recently, a highly efficient arginine transporter ATB0,+ has been described in human tissues. We hypothesize that ATB0,+ is upregulated in colorectal cancer as a means to deliver arginine to iNOS for excess NO production.

Methods: Total RNA was extracted from paired normal and cancer tissue harvested from colectomy specimens of 10 enrolled patients. Expression of ATB0,+ mRNA was determined by semi-quantitative RT-PCR and confirmed by Northern blot. ATB0,+ and iNOS protein expression was determined by immunohistochemistry (IHC). Excess NO was detected by IHC using antibodies against nitrosylated tyrosine residues.

Results: ATB0,+ mRNA showed an 11-fold increase in colorectal cancer by RT-PCR (the 95% lower confidence limit for relative expression was a 6.55 fold increase) and a greater than 10-fold increase by Northern blot. ATBO,+ protein expression showed a corresponding increase by IHC. ATB0,+ and iNOS proteins co-localized in the cell. Cancer tissue showed increased NO levels.

Conclusions: ATB0,+ is significantly up-regulated in colorectal cancer and co-localizes with iNOS. We propose that upregulation of ATB0,+ underlies production of NO in colorectal cancer. Since ATB0,+ has recently been shown to efficiently transport inhibitors of iNOS, this could provide a novel therapeutic strategy in colorectal cancer.