Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells.
Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells.
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DOI：
10.1371/journal.pone.0183578
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Reddy KB
中科院分区：
文献类型：
--
作者：
Yin S;Cheryan VT;Xu L;Rishi AK;Reddy KB
与其他乳腺癌亚型相比，患有三阴性乳腺癌（TNBC）的女性预后较差。有几份报告表明非洲裔美国人（AA）和欧洲裔美国人（EA）女性之间乳腺癌结局的种族差异。例如，AA乳腺癌患者的死亡率是EA患者的三倍，尽管AA女性的发病率较低。我们的体外研究表明，源自AA TNBC细胞系的癌症干细胞样细胞（CSC）比源自EA细胞系的CSC具有显著更高的自我更新潜力（乳腺球形成）。与表达管腔A或HER 2的乳腺癌相比，TNBC肿瘤表达高水平的Myc。我们研究了c-Myc过表达对AA和EA衍生的TNBC细胞系中CSC和化疗的影响。与对照组相比，c-Myc在AA衍生的MDA-MB-468（Myc/MDA-468）细胞中的过表达导致CSC的显著增加，并且上皮向间充质转化（EMT）的变化最小。与此相反，在EA衍生的MDA-MB-231（Myc/MDA-231）细胞中过表达c-Myc导致上皮向间充质转化（EMT）增加，与对照组相比CSC增加最小。Myc/MDA-468细胞对标准化疗治疗如iniparib（PARP抑制剂）加顺铂、iniparib、顺铂、紫杉醇和多西他赛具有抗性。然而，Myc/MDA-231细胞表现出EMT变化，对iniparib和顺铂有反应，但对其他药物如iniparib、顺铂、紫杉醇和多西他赛耐药。总的来说，我们的研究结果表明，肿瘤生物学的内在差异可能有助于乳腺癌的差异。
Women with triple negative breast cancer (TNBC) have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA) and European American (EA) women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs) derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation) than CSCs derived from EA cell lines. TNBC tumors express high levels of Myc compared to luminal A or HER2 expressing breast cancers. We studied the effects of c-Myc overexpression on CSCs and chemotherapy in AA, and EA derived TNBC cell line(s). Overexpression of c-Myc in AA derived MDA-MB-468 (Myc/MDA-468) cells resulted in a significant increase in CSCs and with minimal changes in epithelial-to-mesenchymal transition (EMT) compared to the control group. In contrast, overexpression of c-Myc in EA derived MDA-MB-231(Myc/MDA-231) cells led to increased epithelial-to-mesenchymal transition (EMT), with a minimal increase in CSCs compared to the control group. Myc/MDA-468 cells were resistant to standard chemotherapeutic treatments such as iniparib (PARP inhibitor) plus cisplatin, / iniparib, cisplatin, paclitaxel and docetaxel. However, Myc/MDA-231 cells, which showed EMT changes responded to iniparib with cisplatin, but were resistant to other drugs, such as iniparib, cisplatin, paclitaxel and docetaxel. Collectively, our results indicate that intrinsic differences in the tumor biology may contribute to the breast cancer disparities.
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影响因子：
3.7
作者：
Alles MC;Gardiner-Garden M;Nott DJ;Wang Y;Foekens JA;Sutherland RL;Musgrove EA;Ormandy CJ
通讯作者：
Ormandy CJ
影响因子：
45.3
作者：
Liu, Suling;Wicha, Max S.
通讯作者：
Wicha, Max S.
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
DOI：
10.1073/pnas.0912708107
发表时间：
2010-04-13
影响因子：
11.1
作者：
Gatza, Michael L.;Lucas, Joseph E.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.
影响因子：
5.8
作者：
Carey, Lisa A.
通讯作者：
Carey, Lisa A.