Frequent hypermethylation and loss of heterozygosity of the testis derived transcript gene in ovarian cancer
Frequent hypermethylation and loss of heterozygosity of the testis derived transcript gene in ovarian cancer
复制标题
卵巢癌中睾丸来源转录基因的频繁高甲基化和杂合性丧失
DOI：
10.1111/j.1349-7006.2010.01497.x
复制
发表时间：
2010-05-01
期刊：
影响因子：
5.7
通讯作者：
Kong, Beihua
中科院分区：
文献类型：
--
作者：
Qiu, Haifeng;Zhu, Jiezhi;Kong, Beihua
睾丸衍生转录本（TES）是位于人类染色体7 q31上的一个候选抑癌基因，其在卵巢癌中的作用尚不清楚。使用卵巢癌细胞系和组织样本，我们证明了TES基因的杂合性丢失和高甲基化在卵巢癌中发生的频率很高，TES表达与高甲基化或杂合性丢失之间存在显著相关性。我们还检测了5-氮杂-2-脱氧胞苷处理后卵巢癌细胞系A2780中的甲基化。TES的表达水平大幅上调，导致A2780细胞生物学行为发生变化：细胞生长特性受到极大损害，集落形成能力被抑制到很低的水平，凋亡率与对照组相比大幅升高。我们的研究结果表明，TES基因作为一个肿瘤抑制基因的功能，并经常沉默的超甲基化和杂合性丢失在卵巢癌。
Testis derived transcript (TES) is a candidate tumor suppressor gene located at the human chromosome 7q31, and its function in ovarian cancer is still unknown. Using ovarian cancer cell lines and tissue samples, we demonstrated that both loss of heterozygosity and hypermethylation of the TES gene occurred in ovarian cancer at high frequencies, and there were significant correlations between TES expression and hypermethylation or loss of heterozygosity. We also detected methylation in ovarian cancer cell line A2780 after treatment with 5‐aza‐2‐deoxycytidine. The expression level of TES was enormously up‐regulated, then caused changes to the biological behaviors of A2780 cells: cell growth properties were greatly impaired, colony formatting abilities were suppressed to very low levels, and the apoptosis rate was highly raised compared to the control group. Our findings suggest that the TES gene functions as a tumor suppressor gene and is frequently silenced by hypermethylation and loss of heterozygosity in ovarian cancers.