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Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer
1Department of Cell Biology, Institute of Molecular and Cellular Biology, Okayama University Medical School, Okayama 700-8558, Japan.
Abstract:
Dickkopfs (Dkks) are secretory glycoproteins and are important for inducing amphibian head formation. Some Dkks have the ability to antagonize the Wnt proto-oncoprotein, which can promote cell proliferation and transformation when it is mutated or overexpressed. We recently cloned the REIC/Dkk-3 gene, one of the Dkks, and found that expression of the gene was markedly decreased in many human immortalized and tumor-derived cell lines. To further investigate the function of the REIC/Dkk-3 gene in vivo, the gene expression was quantified in 57 surgically-resected non-small cell lung cancer (NSCLC) tissues and their adjacent normal lung tissues by real-time quantitative PCR analysis based on TaqMan methodology. The REIC/Dkk-3 mRNA level was significantly lower in NSCLC tissues than in normal lung tissues. Reduced expression of REIC/Dkk-3 in NSCLC was observed in 36 (63%) of the 57 tumors. Reduced expression of REIC/Dkk-3 was frequently observed in poorly differentiated adenocarcinoma and squamous cell carcinoma. These results indicate that reduced expression of REIC/Dkk-3 may be correlated with rapid cell proliferation in human NSCLC.
Insights
Reduced expression of the REIC/Dkk-3 gene is common in non-small cell lung cancer (NSCLC). This finding suggests a correlation between lower REIC/Dkk-3 levels and the rapid cell proliferation observed in human NSCLC tumors.
Area of Science:
- Molecular Biology
- Oncology
- Developmental Biology
Background:
- Dickkopfs (Dkks) are secretory glycoproteins crucial for amphibian head formation.
- Some Dkks antagonize Wnt signaling, which can drive cell proliferation and transformation when dysregulated.
- The REIC/Dkk-3 gene, a member of the Dkk family, shows decreased expression in human immortalized and tumor cell lines.
Purpose of the Study:
- To investigate the in vivo function of the REIC/Dkk-3 gene.
- To quantify REIC/Dkk-3 gene expression in non-small cell lung cancer (NSCLC) tissues and adjacent normal lung tissues.
Main Methods:
- Real-time quantitative PCR using TaqMan methodology.
- Analysis of gene expression in 57 surgically-resected NSCLC tissues and paired normal lung tissues.
Main Results:
- REIC/Dkk-3 mRNA levels were significantly lower in NSCLC tissues compared to normal lung tissues.
- Reduced REIC/Dkk-3 expression was observed in 63% of the NSCLC tumors analyzed.
- Downregulation of REIC/Dkk-3 was frequently associated with poorly differentiated adenocarcinoma and squamous cell carcinoma.
Conclusions:
- Reduced expression of REIC/Dkk-3 is a common feature in human NSCLC.
- The findings suggest a correlation between decreased REIC/Dkk-3 expression and the rapid cell proliferation characteristic of NSCLC.