Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer.
Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer.
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DOI：
10.1016/j.bbagrm.2015.02.003
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发表时间：
2015-06
影响因子：
4.7
通讯作者：
Mandal, Subhrangsu S.
中科院分区：
文献类型：
--
作者：
Hussain, Imran;Bhan, Arunoday;Ansari, Khairul I.;Deb, Paromita;Bobzean, Samara A. M.;Perrotti, Linda I.;Mandal, Subhrangsu S.
关键词：
HOXC 6是一种与乳腺发育相关的含有同源框的基因，并且在包括乳腺癌和前列腺癌在内的多种癌症中过表达。在此，我们检测了HOXC 6在乳腺癌组织中的表达，并在体外和体内研究了其通过雌二醇（E2）和双酚A（BPA，一种雌激素性内分泌干扰物）的转录调控。我们观察到HOXC 6在乳腺癌组织中差异过表达。E2诱导培养的乳腺癌细胞和Sprague道利大鼠乳腺中HOXC 6的表达。在体外和体内暴露于BPA时也诱导HOXC 6表达。雌激素受体α（ERα）和ER辅助调节因子（如MLL-组蛋白甲基化酶）在暴露于E2或BPA后与HOXC 6启动子结合，导致组蛋白H3 K4-三甲基化、组蛋白乙酰化和HOXC 6启动子处RNA聚合酶II的募集增加。HOXC 6过表达诱导肿瘤生长因子的表达并促进生长3D集落形成，表明其在肿瘤生长中的潜在作用。我们的研究表明，HOXC 6，这是一个关键的球员在乳腺发育，是上调在多个乳腺癌的情况下，并转录调节E2和BPA，在体外和体内。
HOXC6 is a homeobox-containing gene associated with mammary gland development and is overexpressed in variety of cancers including breast and prostate cancers. Here, we have examined the expression of HOXC6 in breast cancer tissue, investigated its transcriptional regulation via estradiol (E2) and bisphenol-A (BPA, an estrogenic endocrine disruptor) in vitro and in vivo. We observed that HOXC6 is differentially over-expressed in breast cancer tissue. E2 induces HOXC6 expression in cultured breast cancer cells and in mammary glands of Sprague Dawley rats. HOXC6 expression is also induced upon exposure to BPA both in vitro and in vivo. Estrogen-receptor-alpha (ERα) and ER-coregulators such as MLL-histone methylases are bound to the HOXC6 promoter upon exposure to E2 or BPA and that resulted in increased histone H3K4-trimethylation, histone acetylation, and recruitment of RNA polymerase II at the HOXC6 promoter. HOXC6 overexpression induces expression of tumor growth factors and facilitates growth 3D-colony formation, indicating its potential roles in tumor growth. Our studies demonstrate that HOXC6, which is a critical player in mammary gland development, is upregulated in multiple cases of breast cancer, and is transcriptionally regulated by E2 and BPA, in vitro and in vivo.
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影响因子：
3.8
作者：
Blair, RM;Fang, H;Sheehan, DM
通讯作者：
Sheehan, DM
DOI：
10.2165/00129785-200404010-00003
发表时间：
2004-01-01
期刊：
American journal of pharmacogenomics : genomics-related research in drug development and clinical practice
影响因子：
--
作者：
Barkhem, Tomas;Nilsson, Stefan;Gustafsson, Jan-Ake
通讯作者：
Gustafsson, Jan-Ake
影响因子：
--
作者：
Ansari, Khairul I.;Kasiri, Sahba;Mandal, Subhrangsu S.
通讯作者：
Mandal, Subhrangsu S.
DOI：
10.1016/j.jsbmb.2014.02.002
发表时间：
2014-05
影响因子：
4.1
作者：
Bhan, Arunoday;Hussain, Imran;Ansari, Khairul I.;Bobzean, Samara A. M.;Perrotti, Linda I.;Mandal, Subhrangsu S.
通讯作者：
Mandal, Subhrangsu S.
影响因子：
3.8
作者：
Bobzean SA;Dennis TS;Perrotti LI
通讯作者：
Perrotti LI