Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation in human breast cancer.
Transcriptional regulation of the p73 gene by Nrf-2 and promoter CpG methylation in human breast cancer.
复制标题
人乳腺癌中 Nrf-2 和启动子 CpG 甲基化对 p73 基因的转录调控
DOI：
10.18632/oncotarget.2230
复制
发表时间：
2014-08-30
期刊：
影响因子：
--
通讯作者：
Guan X
中科院分区：
文献类型：
--
作者：
Lai J;Nie W;Zhang W;Wang Y;Xie R;Wang Y;Gu J;Xu J;Song W;Yang F;Huang G;Cao P;Guan X
为了解启动子甲基化和Nrf-2在乳腺癌发生中对p73的转录调控，ChIP检测表明，Nrf-2可以与两种启动子结合，并在MCF-7细胞系中激活TAp 73和Δ Np 73的转录，Nrf-2基因的敲低导致用sh-Nrf-2以及Nrf-3转染的细胞中TAp 73和Δ Np 73表达的废除。2敲除小鼠模型。然而，我们发现Nrf-2诱导的Δ Np 73表达被5-aza-dC处理消除，从而导致乳腺癌细胞系中Δ Np 73表达下调和TAp 73表达上调。与该模型一致，我们在乳腺癌组织测定中检测到乳腺癌组织中TAp 73表达降低和Δ Np 73表达增加，以及相应的周围非癌组织（NCT）中TAp 73表达增加但Δ Np 73表达降低。TAp 73和Δ Np 73在上述组织阵列中的表达之间存在显著的负相关（P = 0.047），并且在另一组由128个乳腺癌肿瘤组织组成的组中得到验证（P = 0.034）。综上所述，我们的研究结果表明，Nrf-2和启动子甲基化协同控制p73的转录调控，TAp 73和Δ Np 73表达的不平衡表达在乳腺癌的发展中起着关键作用。
To understand the transcriptional regulation of p73 by promoter methylation and Nrf-2 in breast carcinogenesis, ChIP assay indicated that Nrf-2 can bind to both promoters and can activate the transcription of TAp73 and ΔΝp73 in MCF-7 cell line, knockdown of Nrf-2 gene resulted in an abrogation of TAp73 and ΔΝp73 expression in the cells transfected with sh-Nrf-2 as well as Nrf-2 knock out mouse model. However, we found Nrf-2 induced ΔΝp73 expression was abolished with 5-aza-dC treatment, thus lead to a down-regulated ΔΝp73 and an up-regulated TAp73 expression in breast cancer cells lines. Consistent with this model, we detected decreased TAp73 and increased ΔNp73 expression in breast cancer tissue, along with increased TAp73 but decreased ΔNp73 expression in corresponding surrounding noncancerous tissues (NCTs) in a breast cancer tissue assay. A significant inverse correlation was found between TAp73 and ΔNp73 expression in the above tissue-array (P = 0.047) and validated in another set consisting of 128 breast cancer tumor tissue (P = 0.034). Taken together, our findings suggest that Nrf-2 and promoter methylation cooperatively govern the transcriptional regulation of p73, and unbalanced expression of TAp73 and ΔNp73 expression plays a critical role in breast cancer development.
登录
查看更多内容
DOI：
10.1186/bcr2121
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Rodenhiser DI;Andrews J;Kennette W;Sadikovic B;Mendlowitz A;Tuck AB;Chambers AF
通讯作者：
Chambers AF
影响因子：
6.4
作者：
Daskalos, Alexandros;Nikolaidis, Georgios;Liloglou, Triantafillos
通讯作者：
Liloglou, Triantafillos
影响因子：
4.7
作者：
Lantry, LE;Zhang, ZQ;You, M
通讯作者：
You, M
影响因子：
56.9
作者：
Pozniak, CD;Radinovic, S;Miller, FD
通讯作者：
Miller, FD
影响因子：
3.7
作者：
Al-Salihi, Mazin;Yu, Margaret;Fitzpatrick, F. A.
通讯作者：
Fitzpatrick, F. A.