TY - JOUR
T1 - Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer
AU - Park, Jong Chul
AU - Chae, Young Kwang
AU - Son, Choon Hee
AU - Kim, Myoung Sook
AU - Lee, Juna
AU - Ostrow, Kimberly
AU - Sidransky, David
AU - Hoque, Mohammad Obaidul
AU - Moon, Chulso
N1 - Funding Information:
The study was supported in part by the SPORE Grant P50 CA96784-01, Cancer Research Grant from Pyung-Ya Foundation.
PY - 2008/1/11
Y1 - 2008/1/11
N2 - Early detection of lung cancer is challenging due to a lack of adequate biomarkers. To discover novel tumor suppressor genes (TSGs) silenced by aberrant promoter methylation, we analyzed the gene expression profiles of two lung adenocarcinoma cell lines using pharmacologic-unmasking and subsequent microarray-analysis. Among 617 genes upregulated, we selected 30 genes and investigated the methylation status of their promoters by bisulfite sequencing analysis. Aberrant methylation was detected in four genes (CRABP2, NOEY2, T, MAP2K3) in at least one lung adenocarcinoma cell lines. Furthermore, the T promoter was methylated in 60% of primary lung adenocarcinomas versus 13% of non-malignant lung tissues. Conversely, RT-PCR analysis revealed T expression was low in lung tumors, while high in normal tissues. In addition, no non-synonymous mutations related to gene silencing were found. While further analysis is warranted, our results suggest that T has the potential to be a novel candidate TSG in lung cancer.
AB - Early detection of lung cancer is challenging due to a lack of adequate biomarkers. To discover novel tumor suppressor genes (TSGs) silenced by aberrant promoter methylation, we analyzed the gene expression profiles of two lung adenocarcinoma cell lines using pharmacologic-unmasking and subsequent microarray-analysis. Among 617 genes upregulated, we selected 30 genes and investigated the methylation status of their promoters by bisulfite sequencing analysis. Aberrant methylation was detected in four genes (CRABP2, NOEY2, T, MAP2K3) in at least one lung adenocarcinoma cell lines. Furthermore, the T promoter was methylated in 60% of primary lung adenocarcinomas versus 13% of non-malignant lung tissues. Conversely, RT-PCR analysis revealed T expression was low in lung tumors, while high in normal tissues. In addition, no non-synonymous mutations related to gene silencing were found. While further analysis is warranted, our results suggest that T has the potential to be a novel candidate TSG in lung cancer.
KW - Brachyury homologue (mouse)
KW - Lung adenocarcinoma
KW - Non-small-cell lung cancer
KW - Promoter hypermethylation
KW - T gene
KW - Tumor suppressor gene
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U2 - 10.1016/j.bbrc.2007.10.144
DO - 10.1016/j.bbrc.2007.10.144
M3 - Article
C2 - 17980147
AN - SCOPUS:36248939277
SN - 0006-291X
VL - 365
SP - 221
EP - 226
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -