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Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas
C W Schweinfest1, K W Henderson, S Suster
1Laboratory of Molecular Oncology, National Cancer Institute, Frederick, MD 21702-1201.
Abstract:
A cDNA, which we call DRA (for down-regulated in adenoma) has been isolated. Its mRNA is expressed exclusively in normal colon tissue, probably only in the mucosal epithelia. Expression of the DRA gene is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon. The DRA gene appears to be a single-copy gene present on chromosome 7, a chromosome associated with colorectal tumorigenesis. The predicted DRA polypeptide is an 84,500-Da protein that contains charged clusters of amino acids, primarily at the NH2 and COOH termini. Together with potential nuclear targeting motifs, an acidic transcriptional activation domain, and a homeobox domain, these elements suggest a transcription factor or a protein that may interact with transcription factors. Such a function may be consistent with a role in tissue-specific gene expression and/or as a candidate tumor-suppressor gene.
Insights
A novel gene, DRA (down-regulated in adenoma), is highly expressed in normal colon tissue but significantly decreased in colon tumors. This suggests DRA may function as a tumor suppressor in colorectal cancer.
Area of Science:
- Molecular biology
- Genetics
- Cancer research
Background:
- The DRA (down-regulated in adenoma) gene's expression pattern in normal and cancerous colon tissue is largely unknown.
- Understanding genes involved in colorectal tumorigenesis is crucial for developing new diagnostic and therapeutic strategies.
Purpose of the Study:
- To isolate and characterize the DRA gene.
- To investigate the expression levels of DRA in normal colon tissue, adenomas, and adenocarcinomas.
- To predict the function of the DRA protein and its potential role in colorectal cancer.
Main Methods:
- cDNA isolation and characterization.
- mRNA expression analysis using Northern blotting or similar techniques.
- Bioinformatic analysis of the predicted protein sequence and chromosomal location.
Main Results:
- Isolation of the DRA cDNA, with mRNA exclusively expressed in normal colon mucosal epithelia.
- Significantly decreased DRA gene expression observed in colon adenomas and adenocarcinomas.
- DRA gene located on chromosome 7, a region implicated in colorectal cancer.
- Predicted DRA polypeptide (84.5 kDa) possesses features of a transcription factor, including nuclear targeting motifs and a homeobox domain.
Conclusions:
- The DRA gene is down-regulated during colorectal tumorigenesis.
- The predicted function of the DRA protein suggests a role in tissue-specific gene regulation.
- DRA is a candidate tumor-suppressor gene in the colon.