L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma

The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barr...

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Main Authors: Jules Lin, Duna A. Raoof, Dafydd G. Thomas, Joel K. Greenson, Thomas J. Giordano, Gregory S. Robinson, Maureen J. Bourner, Christopher T. Bauer, Mark B. Orringer, David G. Beer
Format: Article
Language:English
Published: Elsevier 2004-01-01
Series:Neoplasia: An International Journal for Oncology Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S147655860480054X
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author Jules Lin
Duna A. Raoof
Dafydd G. Thomas
Joel K. Greenson
Thomas J. Giordano
Gregory S. Robinson
Maureen J. Bourner
Christopher T. Bauer
Mark B. Orringer
David G. Beer
author_facet Jules Lin
Duna A. Raoof
Dafydd G. Thomas
Joel K. Greenson
Thomas J. Giordano
Gregory S. Robinson
Maureen J. Bourner
Christopher T. Bauer
Mark B. Orringer
David G. Beer
author_sort Jules Lin
collection DOAJ
description The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P < .001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P < .05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P < .001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1.
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spelling doaj.art-f5ff3434d01e43dcb8c4df221ab8c1652022-12-21T19:52:12ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022004-01-0161748410.1016/S1476-5586(04)80054-XL-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's AdenocarcinomaJules Lin0Duna A. Raoof1Dafydd G. Thomas2Joel K. Greenson3Thomas J. Giordano4Gregory S. Robinson5Maureen J. Bourner6Christopher T. Bauer7Mark B. Orringer8David G. Beer9Section of General Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USASection of General Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USAPharmacia Corporation, St. Louis, MO, USAPharmacia Corporation, St. Louis, MO, USAPharmacia Corporation, St. Louis, MO, USASection of General Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USASection of General Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USAThe L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P < .001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P < .05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P < .001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1.http://www.sciencedirect.com/science/article/pii/S147655860480054XEsophageal adenocarcinomaL-type amino acid transporter-1amino acid transportersmelphalanchemotherapy
spellingShingle Jules Lin
Duna A. Raoof
Dafydd G. Thomas
Joel K. Greenson
Thomas J. Giordano
Gregory S. Robinson
Maureen J. Bourner
Christopher T. Bauer
Mark B. Orringer
David G. Beer
L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma
Neoplasia: An International Journal for Oncology Research
Esophageal adenocarcinoma
L-type amino acid transporter-1
amino acid transporters
melphalan
chemotherapy
title L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma
title_full L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma
title_fullStr L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma
title_full_unstemmed L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma
title_short L-Type Amino Acid Transporter-1 Overexpression and Melphalan Sensitivity in Barrett's Adenocarcinoma
title_sort l type amino acid transporter 1 overexpression and melphalan sensitivity in barrett s adenocarcinoma
topic Esophageal adenocarcinoma
L-type amino acid transporter-1
amino acid transporters
melphalan
chemotherapy
url http://www.sciencedirect.com/science/article/pii/S147655860480054X
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