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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Elsevier
2004-01-01
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Series: | Neoplasia: An International Journal for Oncology Research |
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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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language | English |
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publishDate | 2004-01-01 |
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series | Neoplasia: An International Journal for Oncology Research |
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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