Upregulation of the amino acid transporter ATB0,+ (SLC6A14) in colorectal cancer and metastasis in humans

Naren Gupta, Seiji Miyauchi, Robert Martindale, Anne V. Herdman, Robert Podolsky, Katsuya Miyake, Sela Mager, Puttur D. Prasad, Malliga E. Ganapathy, Vadivel Ganapathy

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

ATB0,+ (SLC6A14) is a Na+/Cl--coupled arginine transporter expressed at low levels in normal colon. Arginine is an essential amino acid for tumor cells. Arginine is also the substrate for nitric oxide synthases (NOSs). Since arginine and arginine-derived nitric oxide (NO) play a critical role in cancer, we examined the expression of ATB0,+ in colorectal cancer. Paired normal and cancer tissues from colectomy specimens of 10 patients with colorectal cancer and from the liver tissue of one patient with hepatic metastasis from a colonic primary were used for the analysis of the levels of ATB0,+ mRNA, inducible NOS (iNOS) mRNA and the corresponding proteins. Tissues samples from the colon, liver, and lymph nodes of an additional patient with metastatic colon cancer were analyzed for ATB 0,+ protein alone. We also examined the levels of nitrotyrosylated proteins. The ATB0,+ mRNA increased 22.9 ± 3.0-fold in colorectal cancer compared to normal tissue and the increase was evident in each of the 10 cases examined. iNOS mRNA increased 5.2 ± 1.1-fold in cancer specimens. The changes in mRNA levels were associated with an increase in ATB0,+, iNOS, and nitrotyrosylated proteins. The increased expression of ATB0,+ and iNOS was also demonstrated in liver and lymph node specimens with metastases from colonic primaries. This study strongly suggests that the upregulation of ATB0,+ may have a pathogenic role in colorectal cancer. Since ATB0,+ is a versatile transporter not only for arginine but also for several drugs including NOS inhibitors, these findings have significant clinical and therapeutic relevance.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1741
Issue number1-2
DOIs
StatePublished - Jun 30 2005
Externally publishedYes

Fingerprint

Amino Acid Transport Systems
Arginine
Colorectal Neoplasms
Up-Regulation
Neoplasm Metastasis
Messenger RNA
Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Liver
Neoplasms
Colon
Lymph Nodes
Proteins
Essential Amino Acids
Colectomy
Liver Neoplasms
Colonic Neoplasms
Nitric Oxide
Pharmaceutical Preparations

Keywords

  • Amino acid transporter ATB
  • Cancer
  • Colon
  • Nitric oxide
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

Upregulation of the amino acid transporter ATB0,+ (SLC6A14) in colorectal cancer and metastasis in humans. / Gupta, Naren; Miyauchi, Seiji; Martindale, Robert; Herdman, Anne V.; Podolsky, Robert; Miyake, Katsuya; Mager, Sela; Prasad, Puttur D.; Ganapathy, Malliga E.; Ganapathy, Vadivel.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1741, No. 1-2, 30.06.2005, p. 215-223.

Research output: Contribution to journalArticle

Gupta, N, Miyauchi, S, Martindale, R, Herdman, AV, Podolsky, R, Miyake, K, Mager, S, Prasad, PD, Ganapathy, ME & Ganapathy, V 2005, 'Upregulation of the amino acid transporter ATB0,+ (SLC6A14) in colorectal cancer and metastasis in humans', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1741, no. 1-2, pp. 215-223. https://doi.org/10.1016/j.bbadis.2005.04.002
Gupta, Naren ; Miyauchi, Seiji ; Martindale, Robert ; Herdman, Anne V. ; Podolsky, Robert ; Miyake, Katsuya ; Mager, Sela ; Prasad, Puttur D. ; Ganapathy, Malliga E. ; Ganapathy, Vadivel. / Upregulation of the amino acid transporter ATB0,+ (SLC6A14) in colorectal cancer and metastasis in humans. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2005 ; Vol. 1741, No. 1-2. pp. 215-223.
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AU - Podolsky, Robert

AU - Miyake, Katsuya

AU - Mager, Sela

AU - Prasad, Puttur D.

AU - Ganapathy, Malliga E.

AU - Ganapathy, Vadivel

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