The CCL2 chemokine is a negative regulator of autophagy and necrosis in luminal B breast cancer cells.
The CCL2 chemokine is a negative regulator of autophagy and necrosis in luminal B breast cancer cells.
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DOI：
10.1007/s10549-015-3324-4
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发表时间：
2015-04
影响因子：
3.8
通讯作者：
Cheng, Nikki
中科院分区：
文献类型：
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作者：
Fang, Wei Bin;Yao, Min;Jokar, Iman;Alhakamy, Nabil;Berkland, Cory;Chen, Jin;Brantley-Sieders, Dana;Cheng, Nikki
管腔A型和B型乳腺癌是女性中诊断出的最常见的乳腺癌形式。与管腔A型乳腺癌患者相比，管腔B型乳腺癌患者的疾病复发率增加，总体生存率降低。调节管腔B亚型的机制仍然知之甚少。趋化因子CCL 2在乳腺癌中过表达，与患者预后不良相关。本研究的目的是确定CCL 2表达在管腔型B乳腺癌细胞中的作用。对乳腺组织、形成管腔B样病变的MMTV-PyVmT和MMTV-Neu转基因乳腺肿瘤进行免疫染色以检测CCL 2表达。为了确定CCL 2在乳腺癌细胞中的作用，使用与siRNA非共价交联的达特细胞穿透肽（Ca-TAT/siRNA）沉默乳腺肿瘤组织和细胞中的CCL 2基因表达。通过ELISA和流式细胞术检测CCL 2表达。通过流式细胞术、免疫细胞化学和荧光显微镜分析细胞生长和存活。与正常乳腺组织或管腔A型乳腺肿瘤相比，管腔B型乳腺肿瘤、MMTV-PyVmT和MMTV-Neu乳腺肿瘤中CCL 2表达显著增加。Ca-TAT递送CCL 2 siRNA显著降低PyVmT乳腺肿瘤中的CCL 2表达，并降低细胞增殖和存活。PyVmT癌细胞或BT 474 luminal B乳腺癌细胞中的CCL 2基因沉默降低了与增加的坏死和自噬相关的细胞生长和活力。CCL 2表达在管腔型B乳腺癌细胞中过表达，并且通过抑制坏死和自噬来调节细胞生长和存活是重要的。
Luminal A and B breast cancers are the most prevalent forms of breast cancer diagnosed in women. Compared to luminal A breast cancer patients, patients with luminal B breast cancers experience increased disease recurrence and lower overall survival. The mechanisms that regulate the luminal B subtype remain poorly understood. The chemokine CCL2 is overexpressed in breast cancer, correlating with poor patient prognosis. The purpose of this study was to determine the role of CCL2 expression in luminal B breast cancer cells. Breast tissues, MMTV-PyVmT and MMTV-Neu transgenic mammary tumors forming luminal B-like lesions, were immunostained for CCL2 expression. To determine the role of CCL2 in breast cancer cells, CCL2 gene expression was silenced in mammary tumor tissues and cells using TAT cell-penetrating peptides non-covalently cross linked to siRNAs (Ca-TAT/siRNA). CCL2 expression was examined by ELISA and flow cytometry. Cell growth and survival were analyzed by flow cytometry, immunocytochemistry, and fluorescence microscopy. CCL2 expression was significantly increased in luminal B breast tumors, MMTV-PyVmT and MMTV-Neu mammary tumors, compared or normal breast tissue or luminal A breast tumors. Ca-TAT delivery of CCL2 siRNAs significantly reduced CCL2 expression in PyVmT mammary tumors, and decreased cell proliferation and survival. CCL2 gene silencing in PyVmT carcinoma cells or BT474 luminal B breast cancer cells decreased cell growth and viability associated with increased necrosis and autophagy. CCL2 expression is overexpressed in luminal B breast cancer cells and is important for regulating cell growth and survival by inhibiting necrosis and autophagy.
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影响因子：
--
作者：
Haringman, Jasper J.;Gerlag, Danielle M.;Tak, Paul P.
通讯作者：
Tak, Paul P.
影响因子：
11.2
作者：
Guerriero, Jennifer L.;Ditsworth, Dara;Zong, Wei-Xing
通讯作者：
Zong, Wei-Xing
影响因子：
4.8
作者：
Fang, Wei Bin;Jokar, Iman;Cheng, Nikki
通讯作者：
Cheng, Nikki
影响因子：
8
作者：
Bugge, TH;Lund, LR;Degen, JL
通讯作者：
Degen, JL
影响因子：
11.5
作者：
Amaravadi, Ravi K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.