Involvement of Epithelial Cell Transforming Sequence-2 Oncoantigen in Lung and Esophageal Cancer Progression
Purpose: This study aims to isolate potential molecular targets for diagnosis, treatment, and/or prevention of lung and esophageal carcinomas. Experimental Design: We screened for genes that were frequently overexpressed in the tumors through gene expression profile analyses of 101 lung cancers and...
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Published in | Clinical cancer research Vol. 15; no. 1; pp. 256 - 266 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for Cancer Research
01.01.2009
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: This study aims to isolate potential molecular targets for diagnosis, treatment, and/or prevention of lung and esophageal
carcinomas.
Experimental Design: We screened for genes that were frequently overexpressed in the tumors through gene expression profile analyses of 101 lung
cancers and 19 esophageal squamous cell carcinomas (ESCC) by cDNA microarray consisting of 27,648 genes or expressed sequence
tags. In this process, we identified epithelial cell transforming sequence 2 ( ECT2 ) as a candidate. Tumor tissue microarray was applied to examine the expression of ECT2 protein in 242 archived non–small-cell
lung cancers (NSCLC) and 240 ESCC specimens and to investigate its prognostic value. A role of ECT2 in lung and esophageal
cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of ECT2 in
mammalian cells was examined using Matrigel assays.
Results: Northern blot and immunohistochemical analyses detected expression of ECT2 only in testis among 23 normal tissues. Immunohistochemical
staining showed that a high level of ECT2 expression was associated with poor prognosis for patients with NSCLC ( P = 0.0004) as well as ESCC ( P = 0.0088). Multivariate analysis indicated it to be an independent prognostic factor for NSCLC ( P = 0.0005). Knockdown of ECT2 expression by small interfering RNAs effectively suppressed lung and esophageal cancer cell growth. In addition, induction
of exogenous expression of ECT2 in mammalian cells promoted cellular invasive activity.
Conclusions: ECT2 cancer-testis antigen is likely to be a prognostic biomarker in clinic and a potential therapeutic target for the development
of anticancer drugs and cancer vaccines for lung and esophageal cancers. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-08-1672 |