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September 2012 Volume 28 Issue 3

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Article

c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells

  • Authors:
    • Keitaro Hayashi
    • Promsuk Jutabha
    • Hitoshi Endou
    • Naohiko Anzai
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan, J-Pharma Co., Ltd., 2-16-8 Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan
  • Pages: 862-866
    |
    Published online on: June 20, 2012
       https://doi.org/10.3892/or.2012.1878
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Abstract

Tumor cells take up a massive amount of nutrition compared to normal cells for increased metabolism. Therefore, special transporters for organic materials are required to satisfy the powerful consumption of nutrition in tumor cells. L-type amino acid transporter 1 (LAT1) incorporates large neutral amino acids, most of which are also categorized as essential amino acids, into cells in a Na+-independent manner. Because of its high expression levels in a variety of cancer cells, it is speculated that LAT1 functions as a key transporter for highly effective delivery of essential amino acids into cancer cells. In this regard, LAT1 inhibitor is expected to have clinical benefit for cancer therapy. However, the molecular mechanism of enrichment of LAT1 in cancer cells remains poorly understood. Here, we show that a proto-oncogene, c-Myc, is a critical positive regulator of LAT1 expression in MIA Paca-2 human pancreatic cancer cells. The uptake of leucine, a representative neutral amino acid, was strictly dependent on LAT1 in MIA Paca-2 cells, and siRNA-mediated knockdown of LAT1 inhibited cell proliferation. Diminished c-Myc expression with siRNA resulted in severe reduction of LAT1 protein levels as well as mRNA levels, which, in turn, led to a significant defect of leucine incorporation. The LAT1 promoter has a canonical c-Myc binding sequence and overexpression of c-Myc increased LAT1 promoter activity, whereas mutation of c-Myc binding site diminished this effect. Our results suggest biological significance of LAT1 in tumor growth and molecular machinery that could explain why LAT1 is preferentially expressed in cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Hayashi K, Jutabha P, Endou H and Anzai N: c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells. Oncol Rep 28: 862-866, 2012.
APA
Hayashi, K., Jutabha, P., Endou, H., & Anzai, N. (2012). c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells. Oncology Reports, 28, 862-866. https://doi.org/10.3892/or.2012.1878
MLA
Hayashi, K., Jutabha, P., Endou, H., Anzai, N."c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells". Oncology Reports 28.3 (2012): 862-866.
Chicago
Hayashi, K., Jutabha, P., Endou, H., Anzai, N."c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells". Oncology Reports 28, no. 3 (2012): 862-866. https://doi.org/10.3892/or.2012.1878
Copy and paste a formatted citation
x
Spandidos Publications style
Hayashi K, Jutabha P, Endou H and Anzai N: c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells. Oncol Rep 28: 862-866, 2012.
APA
Hayashi, K., Jutabha, P., Endou, H., & Anzai, N. (2012). c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells. Oncology Reports, 28, 862-866. https://doi.org/10.3892/or.2012.1878
MLA
Hayashi, K., Jutabha, P., Endou, H., Anzai, N."c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells". Oncology Reports 28.3 (2012): 862-866.
Chicago
Hayashi, K., Jutabha, P., Endou, H., Anzai, N."c-Myc is crucial for the expression of LAT1 in MIA Paca-2 human pancreatic cancer cells". Oncology Reports 28, no. 3 (2012): 862-866. https://doi.org/10.3892/or.2012.1878
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