Significance of maspin tumor suppressor genes in human tumors

癌症相关的DNA低甲基化与癌症相关的高甲基化一样普遍，但DNA低甲基化在癌症发生中的生物学意义尚不清楚。maspin（乳腺丝氨酸蛋白酶抑制剂）在癌组织和非癌组织中的表达。已经在几种癌细胞类型中解决了由于表观遗传修饰引起的特异性maspin表达。为了阐明maspin基因在甲状腺癌中的作用，我们研究了启动子区域的甲基化状态及其在人类癌症中的表达。甲基化特异性PCR方法评估其甲基化状态显示出良好的负相关性与其在手术切除标本中的免疫反应性。我们的数据表明，DNA低甲基化导致的Maspin过度表达与甲状腺癌的形态学去分化密切相关。在化生（肠化生）和癌组织中观察到maspin的免疫反应性。这些异常表达是由启动子区表观遗传状态的破坏引起的。异常maspin表达似乎与形态学变化密切相关，如化生，发育不良和去分化，可能是由于表观遗传表达机制的破坏。

Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but the biological significance of DNA hypomethylation in carcinogenesis is less understood. The expression of maspin (mammary serpin) in cancerous and non-cancerous tissues. Paradoxical maspin expression due to epigenetic modification has been addressed in several cancer cell types. To elucidate the role of the maspin gene in thyroid cancer, we studied methylation status in the promoter region and its expression in human cancers. Their methylation status evaluated by the methylation-specific PCR method showed a good inverse correlation with their immunoreactivity in surgically resected specimens. Our data suggest that over-expression of Maspin by DNA hypomethylation is closely associated with morphological dedifferentiation in thyroid cancers. Immunoreactivity for maspin was observed in metaplastic (intestinal metaplasia) and cancerous tissues. There aberrant expression were caused by the disruption of the epigenetic status at the promoter region. Aberrant maspin expression appears to be closely associated with morphological changes such as metaplasia, dysplasia and dedifferentiation, probably as a result of disruption of epigenetic expression mechanisms.