Simizu Siro, Ishida Keisuke, Wierzba Michal K, Sato Taka Aki, Osada Hiroyuki
Antibiotics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Cancer Lett. 2003 Apr 10;193(1):83-9. doi: 10.1016/s0304-3835(02)00719-x.
Heparanase is an endo-beta-D-glucuronidase that can cleave heparan sulfate and has been implicated in tumor angiogenesis and metastasis. Recent studies have demonstrated that overexpression of heparanase in human tumors facilitates their invasion activity, thereby enhancing the metastatic potential of the tumors. We found that heparanase mRNA and heparanase protein were constitutively elevated in some human tumor cell lines and human head and neck tumors. Heparanase mRNA expression was increased in response to treatment with an inhibitor of DNA methylation in cells that normally express low levels of heparanase mRNA. Inhibition of DNA methylation did not enhance heparanase mRNA expression in the presence of cycloheximide. These results suggest that overexpression of heparanase mRNA in cancer cells might not be due to demethylation of the promoter region of the heparanase gene itself, rather the other gene(s), such as transcriptional factors that, in turn, regulate heparanase expression.
乙酰肝素酶是一种内切-β-D-葡糖醛酸酶，可裂解硫酸乙酰肝素，与肿瘤血管生成和转移有关。最近的研究表明，人肿瘤中乙酰肝素酶的过表达促进其侵袭活性，从而增强肿瘤的转移潜能。我们发现，在一些人肿瘤细胞系和人头颈肿瘤中，乙酰肝素酶mRNA和乙酰肝素酶蛋白持续升高。在正常表达低水平乙酰肝素酶mRNA的细胞中，用DNA甲基化抑制剂处理后，乙酰肝素酶mRNA表达增加。在存在环己酰亚胺的情况下，抑制DNA甲基化并未增强乙酰肝素酶mRNA表达。这些结果表明，癌细胞中乙酰肝素酶mRNA的过表达可能并非由于乙酰肝素酶基因本身启动子区域的去甲基化，而是其他基因，如反过来调节乙酰肝素酶表达的转录因子。
