Cell specific CD44 expression in breast cancer requires the interaction of AP-1 and NFκB with a novel cis-element.
Cell specific CD44 expression in breast cancer requires the interaction of AP-1 and NFκB with a novel cis-element.
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乳腺癌中细胞特异性CD44的表达需要AP-1和NFκB与新型的顺式元素的相互作用。
DOI：
10.1371/journal.pone.0050867
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Smith SM;Cai L
乳腺癌包含一个异质性的细胞群体，其中一小部分细胞具有与干细胞相似的特性。乳腺癌干细胞（BCSC）的广泛接受的标志物之一是细胞表面标志物CD 44。作为一种糖蛋白，CD 44参与许多细胞过程，包括细胞粘附、迁移和增殖，使其本质上是促癌的。CD 44表达在BCSC中高度上调，并且与肿瘤发生和转移有关。然而，导致乳腺癌细胞和BCSC中高水平CD 44表达的遗传机制尚不清楚。在这里，我们确定了一种新的顺式元件的CD 44指导基因表达在乳腺癌细胞中的细胞类型特异性的方式。我们进一步鉴定了关键的反式作用因子结合位点和核因子AP-1和NFκB，它们参与细胞特异性CD 44表达的调节。这些发现为CD 44表达的复杂调控机制提供了新的见解，这可能有助于确定针对乳腺癌干细胞和转移性肿瘤的更有效的治疗靶点。
Breast cancers contain a heterogeneous population of cells with a small percentage that possess properties similar to those found in stem cells. One of the widely accepted markers of breast cancer stem cells (BCSCs) is the cell surface marker CD44. As a glycoprotein, CD44 is involved in many cellular processes including cell adhesion, migration and proliferation, making it pro-oncogenic by nature. CD44 expression is highly up-regulated in BCSCs, and has been implicated in tumorigenesis and metastasis. However, the genetic mechanism that leads to a high level of CD44 expression in breast cancer cells and BCSCs is not well understood. Here, we identify a novel cis-element of the CD44 directs gene expression in breast cancer cells in a cell type specific manner. We have further identified key trans-acting factor binding sites and nuclear factors AP-1 and NFκB that are involved in the regulation of cell-specific CD44 expression. These findings provide new insight into the complex regulatory mechanism of CD44 expression, which may help identify more effective therapeutic targets against the breast cancer stem cells and metastatic tumors.
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DOI：
10.1186/bcr1673
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fillmore C;Kuperwasser C
通讯作者：
Kuperwasser C
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
4.8
作者：
Foster, LC;Wiesel, P;Perrella, MA
通讯作者：
Perrella, MA