Antiproliferative activity of REIC/Dkk-3 and its significant down-regulation in non-small-cell lung carcinomas

We recently reported the cloning of the REIC/Dkk-3 gene, whose expression w as shown to be downregulated in many human immortalized and tumor-derived c ell lines [T. Tsuji et al. (2000) Biochem. Biophys. Res. Commun. 268, 20-24 ]. In the present study, we demonstrated that expression of the exogenous R EIC/Dkk-3 gene in tumor cells inhibited cell growth. Furthermore, the level of REIC/Dkk-3 mRNA in normal human cells was lowest in the late G, phase d uring the cell cycle. Then we found that the expression of REIC/Dkk-3 was s ignificantly down-regulated in surgically resected non-small-cell lung carc inomas. We determined the REIC/Dkk-3 locus on chromosome 11p15, where loss of heterozygosity has frequently been observed in human tumors. These findi ngs indicate that REIC/Dkk-3 may function as a tumor suppressor. (C) 2001 A cademic Press.