Mucin 2 (MUC2) modulates the aggressiveness of breast cancer.
Mucin 2 (MUC2) modulates the aggressiveness of breast cancer.
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DOI：
10.1007/s10549-018-4989-2
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发表时间：
2019-01
影响因子：
3.8
通讯作者：
Jacobsen BM
中科院分区：
文献类型：
--
作者：
Astashchanka A;Shroka TM;Jacobsen BM
分泌大量粘液的肿瘤具有化疗抗性，然而，这种抗性的机制尚不清楚。在分泌粘蛋白的乳腺癌中高度表达的一种蛋白质是分泌的粘蛋白，粘蛋白-2（MUC 2）。虽然MUC 2在一些乳腺癌中表达，但它在正常乳腺组织中不存在，暗示它在乳腺癌中。然而，MUC 2对乳腺癌的影响在很大程度上是未知的。本研究检测了MUC 2在调节乳腺癌增殖、化疗反应和转移中的作用。使用患者来源的异种移植物，我们开发了两种新的细胞系，称为BCK 4和PT 12，其表达高水平的MUC 2。为了调节MUC 2水平，将BCK 4和PT 12细胞工程化以表达靶向MUC 2的shRNA（shMUC 2，低MUC 2）或非靶向对照（shCONT，高MUC 2），并在体外和体内测量增殖和凋亡。用GFP-荧光素酶标记具有shCONT或shMUC 2的BCK 4细胞，并在实验转移模型中进行检查;分别通过活体成像和荧光引导的解剖来监测疾病负荷和部位特异性播散。与对照细胞相比，BCK 4和PT 12 shMUC 2细胞在体外和体内的增殖均降低。化疗在表达高MUC 2的对照细胞中诱导最小的凋亡，但在含有低MUC 2的shMUC 2细胞中增加凋亡。实验转移模型显示，当乳腺癌细胞含有低MUC 2与高MUC 2时，疾病负担降低。表皮生长因子（EGF）治疗增加BCK 4细胞中MUC 2的表达; EGF受体抑制剂厄洛替尼消除了这种诱导作用。MUC 2在介导乳腺癌细胞增殖、凋亡和转移中起重要作用。MUC 2在指导乳腺癌患者的治疗和预测预后方面可能很重要。
Tumors that secrete large volumes of mucus are chemotherapy resistant, however, mechanisms underlying this resistance are unknown. One protein highly expressed in mucin secreting breast cancers is the secreted mucin, Mucin-2 (MUC2). While MUC2 is expressed in some breast cancers it is absent in normal breast tissue, implicating it in breast cancer. However, the effects of MUC2 on breast cancer are largely unknown. This study examined the role of MUC2 in modulating breast cancer proliferation, response to chemotherapy and metastasis. Using patient derived xenografts we developed two novel cell lines, called BCK4 and PT12, which express high levels of MUC2. To modulate MUC2 levels, BCK4 and PT12 cells were engineered to express shRNA targeted to MUC2 (shMUC2, low MUC2) or a non-targeting control (shCONT, high MUC2) and proliferation and apoptosis were measured in vitro and in vivo. BCK4 cells with shCONT or shMUC2 were labeled with GFP-luciferase and examined in an experimental metastasis model; disease burden and site specific dissemination were monitored by intravital imaging and fluorescence guided dissection, respectively. Proliferation decreased in BCK4 and PT12 shMUC2 cells versus control cells both in vitro and in vivo. Chemotherapy induced minimal apoptosis in control cells expressing high MUC2 but increased apoptosis in shMUC2 cells containing low MUC2. An experimental metastasis model showed disease burden decreased when breast cancer cells contained low versus high MUC2. Treatment with Epidermal Growth Factor (EGF) increased MUC2 expression in BCK4 cells; this induction was abolished by the EGF-receptor inhibitor, Erlotinib. MUC2 plays an important role in mediating proliferation, apoptosis and metastasis of breast cancer cells. MUC2 may be important in guiding treatment and predicting outcomes in breast cancer patients.
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影响因子：
5.6
作者：
Adsay, NV;Merati, K;Klimstra, DS
通讯作者：
Klimstra, DS
影响因子：
11.2
作者：
Mukhopadhyay, Partha;Chakraborty, Subhankar;Ponnusamy, Moorthy P.;Lakshmanan, Imayavaramban;Jain, Maneesh;Batra, Surinder K.
通讯作者：
Batra, Surinder K.
影响因子：
6.2
作者：
Harrell JC;Shroka TM;Jacobsen BM
通讯作者：
Jacobsen BM
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.
影响因子：
4.8
作者：
Ookawa, K;Kudo, T;Tsuchida, S
通讯作者：
Tsuchida, S