Aberrant methylation of human L- and M-fructose 1,6-bisphosphatase genes in cancer
Aberrant methylation of human L- and M-fructose 1,6-bisphosphatase genes in cancer
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DOI：
10.1016/j.bbrc.2008.10.045
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发表时间：
2008-12-12
影响因子：
3.1
通讯作者：
Eschrich, Klaus
中科院分区：
文献类型：
--
作者：
Bigl, Marina;Jandrig, Burkhard;Eschrich, Klaus
在肝癌、肌肉癌、乳腺癌、乳腺癌和不同的癌细胞系中研究了果糖 1,6-双磷酸酶 (FBPase) 的两种同工酶可能的表观遗传调控。亚硫酸氢盐测序后获得的结果显示，肝脏、肌肉和乳腺组织中两个启动子的 CpG 甲基化不同，这可能与两种酶的细胞类型特异性基因表达有关。在肿瘤细胞系中，用 5-氮杂-脱氧胞苷去甲基化可激活两种同工酶的表达。使用曲古抑菌素 A 对组蛋白脱乙酰酶的额外抑制进一步增加了 FBPase mRNA 浓度。由于癌症通常具有异常的能量代谢并表现出低糖异生表型，因此研究了启动子甲基化是否导致乳腺癌中 FBPase 表达的降低。当比较同一患者的非恶性和恶性组织样本时，观察到 FBPase 启动子甲基化增加与 FBPase mRNA 水平降低之间的相关性。 (C) 2008 Elsevier Inc. 保留所有权利。
A possible epigenetic regulation of the two isoenzymes of fructose 1,6-bisphosphatase (FBPase) was studied in liver, muscle, mamma, breast cancer and in different cancer cell lines. Results obtained after bisulfite sequencing revealed a different CpG methylation of both promoters in liver, muscle and breast tissue which is putatively involved in the cell-type specific gene expression of the two enzymes. In tumor cell lines, demethylation with 5-aza-deoxycytidine activated the expression of both isoenzymes. Additional inhibition of histone deacetylase with trichostatin A further increased FBPase mRNA concentrations. Since cancers typically have an abnormal energy metabolism and exhibit a low gluconeogenic phenotype, it was studied whether promoter methylation contributes to the decreased expression of FBPase in breast cancer. When non-malignant and malignant tissue samples from the same patient were compared a correlation between an increase of FBPase promoter methylation and a decrease of FBPase mRNA levels was observed. (C) 2008 Elsevier Inc. All rights reserved.