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Stimulation of Expression of the Intestinal Glutamine Transporter ATB⁰ in Tumor-Bearing Rats

Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, College of Medicine, 500 University Drive, P.O. Box MC 850, Hershey, PA 17033, USA

Correspondence: Address correspondence and reprint requests to: Ming Pan, MD, PhD; E-mail: mpan{at}psu.edu

Background: Glutamine supplementation ameliorates host catabolic response in tumor bearing states. The purpose of this in vivo study was to investigate intestinal glutamine transport and expression of glutamine transporter ATB⁰ in methyl-cholanthrene (MCA)-sarcoma bearing rats.

Methods: Fisher-344 rats underwent subcutaneous flank implantation of MCA-sarcoma cells (saline as control) and were pair-fed an equal quantity of chow as controls, to account for tumor-induced anorexia, until tumors reached 10 or 20% body weight. Intestinal mucosal brush border membrane [3H]-Glutamine transport was measured. Glutamine transporter ATB⁰ mRNA and protein levels were measured by real-time PCR and western blot techniques, respectively.

Results: Glutamine transport activity across the intestinal brush border membrane (BBM) was 3.7-fold higher in tumor-bearing rats (TBR) than in controls (TBR 153 ± 22.6 vs. Control 41.9 ± 9.7 pmol/mg protein/10s, P < .01). Transporter ATB⁰ mRNA levels were 1.4-fold higher in tumor-bearing rats (Relative value TBR .61 ± .12 vs. Control .43 ± .1, P < .05). A 1.4-fold increase in transporter ATB⁰ protein levels was observed in the tumor-bearing rats (Relative value TBR .52 ± .07 vs. Control .37 ± .04, P < .05). Circulating aortic plasma glutamine levels were 1.3-fold higher in tumor bearing rats ([Glutamine] = .63 ± .02 Control vs. [Glutamine] = .74 ± .01 mmol/l TBR, P < .0001). Portal venous plasma glutamine levels were also higher in tumor bearing rats ([Glutamine] = .47 ± .01 Control vs. [Glutamine] = .60 ± .02 mmol/l TBR, P < .0001).

Conclusion: Intestinal brush border membrane glutamine transport activity, transporter ATB⁰ mRNA and protein levels are up-regulate in tumor-bearing rats.

Key Words: Glutamine • Methyl-cholanthrene sarcoma • Tumor-bearing rat • ATB⁰