Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer.

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.