Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target.
Genes Dev
; 27(2): 197-210, 2013 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-23322301
ABSTRACT
The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma and analyzed DNA-binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation. Integration of these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1. Further cistromic and overexpression analyses indicated that NKX2-1 can cooperate with the forkhead box transcription factor FOXA1 to regulate LMO3 gene expression. RNAi analysis of NKX2-1-amplified cells compared with nonamplified cells demonstrated that LMO3 mediates cell survival downstream from NKX2-1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transcriptional signal transducer in NKX2-1-amplified lung adenocarcinomas.
Full text:
1
Database:
MEDLINE
Main subject:
Transcription Factors
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Nuclear Proteins
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Adenocarcinoma
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Gene Expression Regulation, Neoplastic
/
Adaptor Proteins, Signal Transducing
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LIM Domain Proteins
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Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Year:
2013
Type:
Article