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Correlation Between the Expression of Amino Acid Transporter LAT1 mRNA and the Amount of L - Leucine Transport in Human Cancer Cell Lines

사람 암세포주들에서 아미노산 수송체 LAT1 mRNA 발현과 아미노산 L - Leucine 수송의 상관관계

  • Kim, Do-Kyung (Oral Biology Research Institute, College of Dentistry, Chosun University) ;
  • Song, Soo-Keun (Oral Biology Research Institute, College of Dentistry, Chosun University) ;
  • Kim, In-Jin (Oral Biology Research Institute, College of Dentistry, Chosun University) ;
  • Kook, Joong-Ki (Oral Biology Research Institute, College of Dentistry, Chosun University)
  • 김도경 (조선대학교 치과대학 구강생물학연구소) ;
  • 송수근 (조선대학교 치과대학 구강생물학연구소) ;
  • 김인진 (조선대학교 치과대학 구강생물학연구소) ;
  • 국중기 (조선대학교 치과대학 구강생물학연구소)
  • Published : 2004.11.01

Abstract

Amino acid transporters play an important role in supplying nutrients to normal and cancer cells for cell proliferation. System L is a major transport system responsible for the $Na^+$ -independent, large neutral amino acids including several essential amino acids. L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed presumably to support their continuous growth and proliferation in malignant tumors. In the present study, we have examined the correlation between the expressions of amino acid transporter LAT1 mRNA and its subunit 4F2hc mRNA and the amount of L-leucine transport in various human cancer cell lines. Northern blot analysis have revealed that the 26 human cancer cell lines expressed LAT1 mRNA and 4F2hc mRNA. There were the differences for the levels of LAT1 and 4F2hc mRNA expressions in the 26 human cancer cell lines. The 26 human cancer cell lines transported the L-[$^{14}C$]leucine into the cells via amino acid transporter. In the 26 human cancer cell lines, a linear relationship was observed between the expression of amino acid transporter LAT1 mRNA and the amount of L-leucine transport. Little relationship was observed between the expression of 4F2hc mRNA and the amount of L-leucine transport, but the statistical significance of difference was not detected. These results indicate that the 26 human cancer cell lines express LAT1 mRNA and 4F2hc mRNA and there is the correlation between the expression of amino acid transporter LAT1 mRNA and the amount of L-leucine transport. In addition, specific inhibition of LAT1 in cancer cells will be a new rationale for anti-cancer therapy.

사람의 여러 암세포주들에서 아미노산 수송체 LAT1 및 그 보조인자 4F2hc mRNA의 발현과 LAT1의 대표적 기질인 L-leucine 수송을 조사하여 이들 사이의 상관관계를 밝히기 위해, 암세포주들에서 northern blot analysis 및 uptake 실험 등을 시행하여 다음과 같은 결과를 얻었다. 조사한 26 종류의 사람 암 유래 세포주들에서 LAT1 mRNA의 뚜렷한 발현을 확인할 수 있었으나 그 발현양에는 차이가 있었다. 조사한 26종류의 사람 암 유래 세포주들에서 4F2hc mRNA의 뚜렷한 발현을 확인할 수 있었으며, LAT1의 경우에서와 같이 발현하는 정도가 조금씩 다름을 확인할 수 있었다. 사람의 암 유래 세포주들에서 아미노산 transporter에 의한 L-[$^{14}C$]leucine 수송을 확인할 수 있었다. 사람의 암세포주들에서 LAT1 mRNA의 발현정도가 높을수록 L-[$^{14}C$]leucine의 수송능력이 증가함을 알 수 있었다. 사람의 암세포주들에서 4F2hc mRNA의 발현정도가 높을수록 L-[$^{14}C$]leucine 수송 능력이 증가하는 경향은 보였으나, 통계적인 유의성은 없었다. 본 연구의 결과에 의해 사람 암세포주들에서 아미노산 transporter LAT1의 발현과 아미노산 L-leucine의 수송 사이와의 상관관계를 확인할 수 있었으며, 아미노산 transporter LAT1의 특이적 억제에 의한 암세포의 성장 억제에 관한 또 하나의 방향성을 제시할 수 있을 것으로 사료된다.

Keywords

References

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