BACKGROUND: L-type amino acid transporter 1 (LAT1) is highly expressed in various human neoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Expression of LAT1 mRNA in 54 lung cancer cell lines was examined by RT-PCR. An inhibitor of LAT1, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), was administered to H1395 cell. LAT1 expression was examined in correlation with clinical features and outcome in 51 NSCLC patients. RESULTS: Inhibition of LAT1 by BCH reduced cell viability in H1395 cells. Furthermore, co-administration of gefitinib with BCH reduced the viability of the cells more than either agent alone. Inhibition of LAT1 reduced the level of phosphorylation of mTOR, p70S6K and 4EBP1. LAT1 protein expression was closely associated with wild type EGFR, and was an independent significant factor to predict a poor prognosis. CONCLUSION: Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.
BACKGROUND:L-type amino acid transporter 1 (LAT1) is highly expressed in various humanneoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Expression of LAT1 mRNA in 54 lung cancer cell lines was examined by RT-PCR. An inhibitor of LAT1, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), was administered to H1395 cell. LAT1 expression was examined in correlation with clinical features and outcome in 51 NSCLCpatients. RESULTS: Inhibition of LAT1 by BCH reduced cell viability in H1395 cells. Furthermore, co-administration of gefitinib with BCH reduced the viability of the cells more than either agent alone. Inhibition of LAT1 reduced the level of phosphorylation of mTOR, p70S6K and 4EBP1. LAT1 protein expression was closely associated with wild type EGFR, and was an independent significant factor to predict a poor prognosis. CONCLUSION: Inhibition of LAT1 may be a new rationale to the effective therapy of NSCLC without EGFR mutation.
Authors: Csaba Juhász; Zeina Nahleh; Ian Zitron; Diane C Chugani; Majid Z Janabi; Sudeshna Bandyopadhyay; Rouba Ali-Fehmi; Thomas J Mangner; Pulak K Chakraborty; Sandeep Mittal; Otto Muzik Journal: Nucl Med Biol Date: 2012-03-22 Impact factor: 2.408
Authors: Jeevisha Bajaj; Takaaki Konuma; Nikki K Lytle; Hyog Young Kwon; Jailal N Ablack; Joseph M Cantor; David Rizzieri; Charles Chuah; Vivian G Oehler; Elizabeth H Broome; Edward D Ball; Edward H van der Horst; Mark H Ginsberg; Tannishtha Reya Journal: Cancer Cell Date: 2016-10-27 Impact factor: 31.743
Authors: William R Wikoff; Samir Hanash; Brian DeFelice; Suzanne Miyamoto; Matt Barnett; Yang Zhao; Gary Goodman; Ziding Feng; David Gandara; Oliver Fiehn; Ayumu Taguchi Journal: J Clin Oncol Date: 2015-08-17 Impact factor: 44.544