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Am J Translational Res 2011;3(5):468-478
Original Article
LAT1 expression is closely associated with hypoxic markers and
mTOR in resected non-small cell lung cancer
Kyoichi Kaira, Noboru Oriuchi, Toshiaki Takahashi, Kazuo Nakagawa, Yasuhisa Ohde, Takehiro Okumura,
Haruyasu Murakami, Takehito Shukuya, Hirokazu Kenmotsu, Tateaki Naito, Yoshikatsu Kanai, Masahiro Endo,
Haruhiko Kondo, Takashi Nakajima, and Nobuyuki Yamamoto
Division of Thoracic Oncology, Division of Thoracic Surgery, Division of Diagnostic Radiology, and Division of
Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777,
Japan. Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of
Medicine, Showa-machi, Maebashi, Gunma 371-8511, Japan. Division of Bio-system Pharmacology, Graduate
School of Medicine, Osaka University, Osaka, Japan.
Received September 17, 2011; accepted October 3, 2011; Epub October 7, 2011; Published October 31, 2011
Abstract: Aim: L-type amino acid transporter 1 (LAT1) is known to be highly expressed in various human
neoplasms. However, little is known about how LAT1 is associated with glucose metabolism, hypoxia and
mammalian target of rapamycin (mTOR) signaling pathway in non-small cell lung cancer (NSCLC). The aim of
this study is to evaluate the relationship between LAT1 expression, and hypoxic marker and mTOR pathway in
resected NSCLC. Methods: One hundred and sixty patients were included in this study. Tumors sections were
stained by immunohistochemistry for LAT1, glucose transporter 1 (Glut1), hypoxia inducible factor-1α (HIF-1α),
hexokinase I, vascular endothelial growth factor (VEGF), microvessel density (MVD) by determinate by CD34,
epidermal growth factor receptor (EGFR), Phosphatase and tensin analog (PTEN), phosph-Akt, phosph-mTOR
and phosph-S6K. Results: A positive LAT1 and CD98 expression were recognized in 36.8% (59/160) and 33.7%
(54/160), respectively (p=0.640). LAT1 expression was significantly associated with CD98, hypoxic markers
(Glut1, HIF-1α, hexokinase I, VEGF and CD34) and mTOR pathway (EGFR, a loss of PTEN, p-mTOR and p-S6K),
especially in lung adenocarcinoma (AC). The expression profile of these biomarkers was significantly higher in
non-AC than in AC, but almost these biomarkers were equally expressed between AC (n=16) and non-AC (n=43)
patients with a positive LAT1 expression. Overexpression of LAT1 was closely associated with poor outcome in
patient with AC. Conclusion: LAT1 expression is closely correlated with hypoxic markers and mTOR pathway in
patients with resected NSCLC. (AJTR1109002).
Keywords: LAT1, Hypoxia, mTOR, Glucose transporter, NSCLC
Full Text PDF
Address all correspondence to:
Dr. Kyoichi Kaira
Division of Thoracic Oncology
Shizuoka Cancer Center
1007 Shimonagakubo Nagaizumi-cho Sunto-gun
Shizuoka, 411-8777, Japan
Tel: +81 55 989 5222, Fax:+81 55 989 5634
E-mail: kkaira1970@yahoo.co.jp
Original Article
LAT1 expression is closely associated with hypoxic markers and
mTOR in resected non-small cell lung cancer
Kyoichi Kaira, Noboru Oriuchi, Toshiaki Takahashi, Kazuo Nakagawa, Yasuhisa Ohde, Takehiro Okumura,
Haruyasu Murakami, Takehito Shukuya, Hirokazu Kenmotsu, Tateaki Naito, Yoshikatsu Kanai, Masahiro Endo,
Haruhiko Kondo, Takashi Nakajima, and Nobuyuki Yamamoto
Division of Thoracic Oncology, Division of Thoracic Surgery, Division of Diagnostic Radiology, and Division of
Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777,
Japan. Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of
Medicine, Showa-machi, Maebashi, Gunma 371-8511, Japan. Division of Bio-system Pharmacology, Graduate
School of Medicine, Osaka University, Osaka, Japan.
Received September 17, 2011; accepted October 3, 2011; Epub October 7, 2011; Published October 31, 2011
Abstract: Aim: L-type amino acid transporter 1 (LAT1) is known to be highly expressed in various human
neoplasms. However, little is known about how LAT1 is associated with glucose metabolism, hypoxia and
mammalian target of rapamycin (mTOR) signaling pathway in non-small cell lung cancer (NSCLC). The aim of
this study is to evaluate the relationship between LAT1 expression, and hypoxic marker and mTOR pathway in
resected NSCLC. Methods: One hundred and sixty patients were included in this study. Tumors sections were
stained by immunohistochemistry for LAT1, glucose transporter 1 (Glut1), hypoxia inducible factor-1α (HIF-1α),
hexokinase I, vascular endothelial growth factor (VEGF), microvessel density (MVD) by determinate by CD34,
epidermal growth factor receptor (EGFR), Phosphatase and tensin analog (PTEN), phosph-Akt, phosph-mTOR
and phosph-S6K. Results: A positive LAT1 and CD98 expression were recognized in 36.8% (59/160) and 33.7%
(54/160), respectively (p=0.640). LAT1 expression was significantly associated with CD98, hypoxic markers
(Glut1, HIF-1α, hexokinase I, VEGF and CD34) and mTOR pathway (EGFR, a loss of PTEN, p-mTOR and p-S6K),
especially in lung adenocarcinoma (AC). The expression profile of these biomarkers was significantly higher in
non-AC than in AC, but almost these biomarkers were equally expressed between AC (n=16) and non-AC (n=43)
patients with a positive LAT1 expression. Overexpression of LAT1 was closely associated with poor outcome in
patient with AC. Conclusion: LAT1 expression is closely correlated with hypoxic markers and mTOR pathway in
patients with resected NSCLC. (AJTR1109002).
Keywords: LAT1, Hypoxia, mTOR, Glucose transporter, NSCLC
Full Text PDF
Address all correspondence to:
Dr. Kyoichi Kaira
Division of Thoracic Oncology
Shizuoka Cancer Center
1007 Shimonagakubo Nagaizumi-cho Sunto-gun
Shizuoka, 411-8777, Japan
Tel: +81 55 989 5222, Fax:+81 55 989 5634
E-mail: kkaira1970@yahoo.co.jp
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