Involvement of epithelial cell transforming sequence-2 oncoantigen in lung and esophageal cancer progression.
OBJECTIVE
This study aims to isolate potential molecular targets for diagnosis, treatment, and/or prevention of lung and esophageal carcinomas.


METHODS
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.
Hirata
Daizaburo
D
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Yamabuki
Takumi
T
Miki
Daiki
D
Ito
Tomoo
T
Tsuchiya
Eiju
E
Fujita
Masahiro
M
Hosokawa
Masao
M
Chayama
Kazuaki
K
Nakamura
Yusuke
Y
Daigo
Yataro
Y
D000368:Aged; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*
D015415:Biomarkers; C489850:ECT2 protein, human; D011518:Proto-Oncogene Proteins