Zeranol down-regulates p53 expression in primary cultured human breast cancer epithelial cells through epigenetic modification.
Zeranol down-regulates p53 expression in primary cultured human breast cancer epithelial cells through epigenetic modification.
复制标题
DOI：
10.3390/ijms12031519
复制
发表时间：
2011
影响因子：
5.6
通讯作者：
Lin YC
中科院分区：
文献类型：
--
作者：
Ye W;Xu P;Jen R;Feng E;Zhong S;Li H;Lin SH;Liu JY;Lin YC
流行病学研究表明，有许多与乳腺癌相关的危险因素。通过表观遗传改变沉默肿瘤抑制基因在乳腺癌的发生、促进和进展中起着关键作用。Zeranol (Z)作为一种生长促进剂，已获得FDA批准，在美国被广泛用于促进肉牛生长。然而，使用Z作为生长促进剂的安全性仍在争论中。为了提供更多的证据来阐明这一关键的健康问题，本研究利用MTS法、RT-PCR和Western blot分析，研究了Z对从同一患者分离的原代培养的人正常乳腺上皮细胞和癌性乳腺上皮细胞（分别为PCHNBECs和PCHBCECs）增殖的影响。我们还对可能涉及的机制进行了调查。我们的研究结果表明，Z比PCHNBEC更能促进PCHBCEC的生长。Z对PCHBCECs和PCHBCECs的刺激作用可能是通过在mRNA和蛋白水平上下调肿瘤抑制基因p53的表达来介导的。进一步的研究表明，与pchbecs相比，Z处理后PCHBCECs中DNA甲基转移酶1 mRNA的表达和蛋白水平均上调，这表明Z参与了PCHBCECs中p53基因表达调控的表观遗传修饰。我们的实验结果表明，在乳腺癌的发展中，Z可能对健康产生不利影响。我们的实验室正在进行进一步的研究。
Epidemiological studies have suggested that there are many risk factors associated with breast cancer. Silencing tumor suppressor genes through epigenetic alterations play critical roles in breast cancer initiation, promotion and progression. As a growth promoter, Zeranol (Z) has been approved by the FDA and is widely used to enhance the growth of beef cattle in the United States. However, the safety of Z use as a growth promoter is still under debate. In order to provide more evidence to clarify this critical health issue, the current study investigated the effect of Z on the proliferation of primary cultured human normal and cancerous breast epithelial cells (PCHNBECs and PCHBCECs, respectively) isolated from the same patient using MTS assay, RT-PCR and Western blot analysis. We also conducted an investigation regarding the mechanisms that might be involved. Our results show that Z is more potent to stimulate PCHBCEC growth than PCHNBEC growth. The stimulatory effects of Z on PCHBCECs and PCHBCECs may be mediated by its down-regulating expression of the tumor suppressor gene p53 at the mRNA and protein levels. Further investigation showed that the expression of DNA methylatransferase 1 mRNA and protein levels is up-regulated by treatment with Z in PCHBCECs as compared to PCHNBECs, which suggests a role of Z in epigenetic modification involved in the regulation of p53 gene expression in PCHBCECs. Our experimental results imply the potentially adverse health effect of Z in breast cancer development. Further study is continuing in our laboratory.
登录
查看更多内容
影响因子：
3.5
作者：
Huang, THM;Perry, MR;Laux, DE
通讯作者：
Laux, DE
影响因子：
4.7
作者：
Ai, Lingbao;Tao, Qian;Robertson, Keith D.
通讯作者：
Robertson, Keith D.
影响因子：
3.8
作者：
Liu, SL;Kulp, SK;Lin, YC
通讯作者：
Lin, YC
影响因子：
3.6
作者：
Lai, H;Lin, L;Meng, L
通讯作者：
Meng, L
DOI：
10.1016/s0960-0760(00)00040-6
发表时间：
2000-01-01
影响因子：
4.1
作者：
Chetrite, GS;Cortes-Prieto, J;Pasqualini, JR
通讯作者：
Pasqualini, JR