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Expression of drs mRNA in human lung adenocarcinomas
Misuzu Shimakage1, Koji Takami, Ken Kodama
1Clinical Research Institute, Osaka National Hospital, Japan.
Abstract:
The drs gene was originally isolated from a rat primary embryo fibroblast cDNA library as a suppressor gene against v-src transformation. We have previously shown that expression of drs mRNA was markedly reduced in a variety of human cancer cell lines, including those of the colon, bladder, and ovary. Furthermore, introduction of drs cDNA by retrovirus vector into these cancer cell lines caused suppression of anchorage-independent growth without affecting cell proliferation. These findings suggest that down-regulation of drs mRNA is closely correlated with expression of malignant phenotypes in development of human cancers. To clarify the correlation between down-regulation of drs mRNA and malignant tumor formation in human tumor tissues, we examined the expression of drs mRNA in well-differentiated, moderately differentiated, and poorly differentiated lung adenocarcinoma tissues by in situ mRNA hybridization. The results clearly indicated that expression of drs mRNA was markedly reduced in 5 of 5 poorly differentiated lung adenocarcinomas examined but significantly expressed in normal lung tissues and 5 of 7 moderately-differentiated and 3 of 5 well-differentiated lung adenocarcinoma tissues. Neither gross deletion nor rearrangement of the drs genome was detected in these tissues. Down-regulation of drs mRNA was also observed in human lung adenocarcinoma cell lines derived from poorly differentiated adenocarcinomas. Our results suggest that down-regulation of drs mRNA is correlated with a poor degree of differentiation and progression of lung adenocarcinoma.
Insights
The drs gene, a cancer suppressor, is significantly reduced in poorly differentiated lung adenocarcinomas. This down-regulation correlates with tumor progression and poor differentiation, suggesting drs
Area of Science:
- Molecular Biology
- Oncology
- Gene Expression
Background:
- The drs gene was identified as a suppressor of v-src transformation.
- Reduced drs mRNA expression is observed in various human cancer cell lines.
- Drs cDNA introduction suppresses anchorage-independent growth in cancer cells.
Purpose of the Study:
- To investigate the correlation between drs mRNA down-regulation and malignant tumor formation in human lung adenocarcinoma tissues.
- To examine drs mRNA expression levels in different grades of lung adenocarcinoma differentiation.
Main Methods:
- In situ mRNA hybridization was used to analyze drs mRNA expression in lung adenocarcinoma tissues.
- Analysis included well-differentiated, moderately differentiated, and poorly differentiated tissues.
- Genomic analysis for drs gene deletion or rearrangement was performed.
Main Results:
- Drs mRNA expression was markedly reduced in all 5 poorly differentiated lung adenocarcinomas.
- Drs mRNA was significantly expressed in normal lung tissues and some well- and moderately-differentiated adenocarcinomas.
- No gross deletion or rearrangement of the drs genome was detected.
Conclusions:
- Down-regulation of drs mRNA is strongly correlated with poor differentiation in lung adenocarcinoma.
- Reduced drs mRNA expression is linked to the progression of lung adenocarcinoma.
- Drs gene expression may serve as a biomarker for lung adenocarcinoma progression.