Tsuji T, Nozaki I, Miyazaki M, Sakaguchi M, Pu H, Hamazaki Y, Iijima O, Namba M
Department of Cell Biology, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Biochem Biophys Res Commun. 2001 Nov 23;289(1):257-63. doi: 10.1006/bbrc.2001.5972.
We recently reported the cloning of the REIC/Dkk-3 gene, whose expression was shown to be down-regulated in many human immortalized and tumor-derived cell lines [T. Tsuji et al. (2000) Biochem. Biophys. Res. Commun. 268, 20-24]. In the present study, we demonstrated that expression of the exogenous REIC/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(1) phase during the cell cycle. Then we found that the expression of REIC/Dkk-3 was significantly down-regulated in surgically resected non-small-cell lung carcinomas. We determined the REIC/Dkk-3 locus on chromosome 11p15, where loss of heterozygosity has frequently been observed in human tumors. These findings indicate that REIC/Dkk-3 may function as a tumor suppressor.
我们最近报道了REIC/Dkk-3基因的克隆，该基因的表达在许多人类永生化细胞系和肿瘤衍生细胞系中被发现下调[T. Tsuji等人（2000年），《生物化学与生物物理研究通讯》268卷，20 - 24页]。在本研究中，我们证明了肿瘤细胞中外源REIC/Dkk-3基因的表达抑制细胞生长。此外，正常人类细胞中REIC/Dkk-3 mRNA的水平在细胞周期的G(1)晚期最低。然后我们发现，在手术切除的非小细胞肺癌中，REIC/Dkk-3的表达显著下调。我们确定了11号染色体p15上的REIC/Dkk-3基因座，在人类肿瘤中经常观察到该区域的杂合性缺失。这些发现表明REIC/Dkk-3可能作为一种肿瘤抑制因子发挥作用。
