TOX3 is expressed in mammary ER(+) epithelial cells and regulates ER target genes in luminal breast cancer.
TOX3 is expressed in mammary ER(+) epithelial cells and regulates ER target genes in luminal breast cancer.
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DOI：
10.1186/s12885-015-1018-2
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发表时间：
2015-01-30
期刊：
影响因子：
3.8
通讯作者：
Kaye J
中科院分区：
文献类型：
--
作者：
Seksenyan A;Kadavallore A;Walts AE;de la Torre B;Berel D;Strom SP;Aliahmad P;Funari VA;Kaye J
一个乳腺癌易感位点已被定位为编码TOX3的基因。关于TOX3在乳腺癌或乳腺中的表达模式或生物学作用知之甚少。在这里，我们分析了TOX3在小鼠和人类乳腺以及乳腺癌分子亚型中的表达，并评估了其改变乳腺癌细胞生物学的能力。我们采用细胞分选策略，随后采用实时荧光定量PCR技术，研究了TOX3基因在小鼠乳腺中的表达。为了研究该核蛋白在人乳腺和乳腺肿瘤中的表达，我们制备了人TOX3特异性的兔单克隆抗体。我们在体外对MCF7、BT474和MDA-MB-231细胞系进行了研究，研究了TOX3调控对乳腺癌细胞基因表达的影响。我们发现TOX3在雌激素受体阳性的乳腺上皮细胞中表达，包括祖细胞。一组乳腺癌肿瘤也高表达TOX3，在B腔乳腺癌中，高表达TOX3与预后不良相关。我们还证明了TOX3能够改变MCF7腔内乳腺癌细胞中的基因表达，包括癌症相关基因TFF1和CXCR4。在高表达TOX3的B型乳腺癌细胞系中，敲低TOX3与生长缓慢有关。令人惊讶的是，TOX3也被证明以雌激素不依赖和他莫昔芬不敏感的方式调节TFF1。这些结果表明，这种蛋白的高表达可能在乳腺癌的进展中起着至关重要的作用。这与先前的研究形成鲜明对比，先前的研究表明乳腺癌易感性与TOX3的低表达有关。总之，这些结果表明TOX3有两种不同的作用，一种是在乳腺癌的发生中，可能与TOX3在乳腺上皮细胞祖细胞中的表达有关，另一种是在癌症的进展中。此外，这些结果可以开始阐明已报道的TOX3表达与乳腺癌骨转移的关联，并指出TOX3是雌激素受体介导的基因表达的新调节剂。本文的在线版本（doi:10.1186/s12885-015-1018-2）包含补充材料，授权用户可以使用。
A breast cancer susceptibility locus has been mapped to the gene encoding TOX3. Little is known regarding the expression pattern or biological role of TOX3 in breast cancer or in the mammary gland. Here we analyzed TOX3 expression in murine and human mammary glands and in molecular subtypes of breast cancer, and assessed its ability to alter the biology of breast cancer cells. We used a cell sorting strategy, followed by quantitative real-time PCR, to study TOX3 gene expression in the mouse mammary gland. To study the expression of this nuclear protein in human mammary glands and breast tumors, we generated a rabbit monoclonal antibody specific for human TOX3. In vitro studies were performed on MCF7, BT474 and MDA-MB-231 cell lines to study the effects of TOX3 modulation on gene expression in the context of breast cancer cells. We found TOX3 expression in estrogen receptor-positive mammary epithelial cells, including progenitor cells. A subset of breast tumors also highly expresses TOX3, with poor outcome associated with high expression of TOX3 in luminal B breast cancers. We also demonstrate the ability of TOX3 to alter gene expression in MCF7 luminal breast cancer cells, including cancer relevant genes TFF1 and CXCR4. Knockdown of TOX3 in a luminal B breast cancer cell line that highly expresses TOX3 is associated with slower growth. Surprisingly, TOX3 is also shown to regulate TFF1 in an estrogen-independent and tamoxifen-insensitive manner. These results demonstrate that high expression of this protein likely plays a crucial role in breast cancer progression. This is in sharp contrast to previous studies that indicated breast cancer susceptibility is associated with lower expression of TOX3. Together, these results suggest two different roles for TOX3, one in the initiation of breast cancer, potentially related to expression of TOX3 in mammary epithelial cell progenitors, and another role for this nuclear protein in the progression of cancer. In addition, these results can begin to shed light on the reported association of TOX3 expression and breast cancer metastasis to the bone, and point to TOX3 as a novel regulator of estrogen receptor-mediated gene expression. The online version of this article (doi:10.1186/s12885-015-1018-2) contains supplementary material, which is available to authorized users.
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影响因子：
8
作者：
Guedj, M.;Marisa, L.;de Reynies, A.;Orsetti, B.;Schiappa, R.;Bibeau, F.;MacGrogan, G.;Lerebours, F.;Finetti, P.;Longy, M.;Bertheau, P.;Bertrand, F.;Bonnet, F.;Martin, A. L.;Feugeas, J. P.;Bieche, I.;Lehmann-Che, J.;Lidereau, R.;Birnbaum, D.;Bertucci, F.;de The, H.;Theillet, C.
通讯作者：
Theillet, C.
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1101474
发表时间：
2011-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Aliahmad P;Kadavallore A;de la Torre B;Kappes D;Kaye J
通讯作者：
Kaye J
影响因子：
9.9
作者：
Hua, Sujun;Kallen, Caleb B.;Dhar, Ruby;Baquero, Maria T.;Mason, Christopher E.;Russell, Beth A.;Shah, Parantu K.;Liu, Jiang;Khramtsov, Andrey;Tretiakova, Maria S.;Krausz, Thomas N.;Olopade, Olufunmilayo I.;Rimm, David L.;White, Kevin P.
通讯作者：
White, Kevin P.
影响因子：
9.7
作者：
Alarmo, Emma-Leena;Parssinen, Jenita;Kallioniemi, Anne
通讯作者：
Kallioniemi, Anne