Fukuhara Hiroshi, Kuramochi Masami, Fukami Takeshi, Kasahara Kohtaro, Furuhata Mutsuo, Nobukuni Takahiro, Maruyama Tomoko, Isogai Kana, Sekiya Takao, Shuin Taro, Kitamura Tadaichi, Reeves Roger H, Murakami Yoshinori
Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045.
Jpn J Cancer Res. 2002 Jun;93(6):605-9. doi: 10.1111/j.1349-7006.2002.tb01297.x.
We recently identified TSLC1, a tumor suppressor gene in human lung cancer. Gene silencing by promoter methylation has been observed frequently in adenocarcinoma of the lung, liver, and pancreas. Here, we demonstrate that TSLC1 expression is also absent or markedly reduced in 3 of 4 prostate cancer cell lines. Promoter sequences of TSLC1 were heavily methylated in PPC-1 cells that lacked TSLC1 expression, supporting the idea that promoter methylation is strongly correlated with complete loss of gene expression. Promoter sequences of TSLC1 were also methylated significantly in 7 of 22 (32%) primary prostate cancers. Hypermethylation of the promoter occurred not only in advanced tumors, but also in relatively early-stage tumors. Restoration of TSLC1 expression substantially suppressed tumor formation of PPC-1 cells in nude mice. These findings indicate that alteration of TSLC1 is involved in prostate cancer.
我们最近鉴定出TSLC1，一种人类肺癌中的肿瘤抑制基因。在肺、肝和胰腺的腺癌中，经常观察到启动子甲基化导致的基因沉默。在此，我们证明在4种前列腺癌细胞系中的3种中，TSLC1表达也缺失或显著降低。在缺乏TSLC1表达的PPC-1细胞中，TSLC1的启动子序列高度甲基化，支持了启动子甲基化与基因表达完全丧失密切相关的观点。在22例原发性前列腺癌中的7例（32%）中，TSLC1的启动子序列也有显著甲基化。启动子的高甲基化不仅发生在晚期肿瘤中，也发生在相对早期的肿瘤中。TSLC1表达的恢复显著抑制了PPC-1细胞在裸鼠中的肿瘤形成。这些发现表明TSLC1的改变与前列腺癌有关。
