期刊
NEOPLASIA
卷 6, 期 1, 页码 74-84出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S1476-5586(04)80054-X
关键词
esophageal adenocarcinoma; L-type amino acid transporter-1; amino acid transporters; melphalan; chemotherapy
类别
资金
- NATIONAL CANCER INSTITUTE [T32CA009672, R01CA071606] Funding Source: NIH RePORTER
- NCI NIH HHS [CA71606, R01 CA071606, T32 CA009672-13, T32 CA009672] Funding Source: Medline
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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