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. 2011;3(5):468-78.
Epub 2011 Oct 7.

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, Hirotsugu Kenmotsu, Tateaki Naito, Yoshikatsu Kanai, Masahiro Endo, Haruhiko Kondo, Takashi Nakajima, Nobuyuki Yamamoto

LAT1 expression is closely associated with hypoxic markers and mTOR in resected non-small cell lung cancer

Kyoichi Kaira et al. Am J Transl Res. 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.

Keywords: LAT1; NSCLC; glucose transporter; hypoxia; mTOR.

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Figures

Figure 1
Figure 1
The score of LAT1 (A) and CD98 (B) immunostaining was grade 4 and grade 4, respectively, and their immunostaining pattern was membranous. The immunostaining pattern of p-mTOR (C) and p-S6K (D) was membranous and/or cytoplasmic staining, demonstrating positive staining in almost same areas. But, the positive immunostaining area of p-Akt (E) was not corresponding to that of p-mTOR and p-S6K.
Figure 2
Figure 2
Kaplan-Meier survival analysis for LAT1 expression in all patients (A), adenocarcinoma patients (B) and non-adenocarcinoma (C). Difference in overall survival between subgroups was analyzed using log-rank test.
See this image and copyright information in PMC

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