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

American Journal of Translational Research

Takehito Shukuya¹  Tateaki Naito¹  Nobuyuki Yamamoto¹  Kazuo Nakagawa¹  Haruhiko Kondo¹  Noboru Oriuchi¹  Toshiaki Takahashi¹  Hirotsugu Kenmotsu¹  Yoshikatsu Kanai¹  Yasuhisa Ohde¹  Masahiro Endo¹  Kyoichi Kaira¹  Haruyasu Murakami¹  Takashi Nakajima¹  Takehiro Okumura¹ 

关键词: LAT1;    hypoxia;    mTOR;    glucose transporter;    NSCLC;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Aim: L-type amino acid transporter 1 (LAT1) is known to be highly expressed invarious human neoplasms. However, little is known about how LAT1 is associatedwith glucose metabolism, hypoxia and mammalian target of rapamycin (mTOR)signaling pathway in non-small cell lung cancer (NSCLC). The aim of this studyis to evaluate the relationship between LAT1 expression, and hypoxic marker andmTOR pathway in resected NSCLC. Methods: One hundred and sixty patients wereincluded in this study. Tumors sections were stained by immunohistochemistry forLAT1, 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 factorreceptor (EGFR), Phosphatase and tensin analog (PTEN), phosph-Akt, phosph-mTORand phosph-S6K. Results: A positive LAT1 and CD98 expression were recognized in36.8% (59/160) and 33.7% (54/160), respectively (p=0.640). LAT1expression was significantly associated with CD98, hypoxic markers (Glut1,HIF-1α, hexokinase I, VEGF and CD34) and mTOR pathway (EGFR, a loss ofPTEN, p-mTOR and p-S6K), especially in lung adenocarcinoma (AC). The expressionprofile of these biomarkers was significantly higher in non-AC than in AC, butalmost these biomarkers were equally expressed between AC (n=16) andnon-AC (n=43) patients with a positive LAT1 expression. Overexpression ofLAT1 was closely associated with poor outcome in patient with AC. Conclusion:LAT1 expression is closely correlated with hypoxic markers and mTOR pathway inpatients with resected NSCLC.

【 授权许可】

Unknown