Androgen receptor and heat shock protein 27 co-regulate the malignant potential of molecular apocrine breast cancer.
Androgen receptor and heat shock protein 27 co-regulate the malignant potential of molecular apocrine breast cancer.
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DOI：
10.1186/s13046-018-0762-y
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发表时间：
2018-04-27
期刊：
影响因子：
--
通讯作者：
Niu Y
中科院分区：
文献类型：
--
作者：
Liu X;Feng C;Liu J;Cao L;Xiang G;Liu F;Wang S;Jiao J;Niu Y
雄激素受体（AR）的表达是大汗腺乳腺癌（MABC）最显著的特征。我们在这里报告的机制，AR在调节MABC的行为。本研究中使用了MABC细胞系MDA-MB-453和非MABC细胞系MCF 7。双氢睾酮（DHT）和热休克蛋白27（HSP 27）对细胞增殖的影响进行了定量使用细胞计数试剂盒-8（CCK 8）和克隆形成试验在体外和异种移植肿瘤模型在体内。使用蛋白质印迹、qPCR和免疫荧光测定分析AR和HSP 27的表达。通过免疫共沉淀（Co-IP）检测AR和HSP 27的复合物。在MDA-MB-453细胞中，DHT促进细胞增殖，刺激AR和HSP 27从细胞质易位到细胞核，而在MCF 7细胞中，DHT抑制细胞生长，仅AR易位到细胞核。HSP 27基因敲低可降低MDA-MB-453细胞的增殖能力，但可被DHT所挽救，而HSP 27和DHT对MCF 7细胞的增殖有协同作用。HSP 27磷酸化是AR转位入核的先决条件，尤其是丝氨酸82的磷酸化。此外，DHT刺激MDA-MB-453细胞的致瘤性和转移能力，而HSP 27敲低则降低肿瘤形成率并诱导细胞凋亡。结果提示，HSP 27参与了AR对MABC恶性行为的调控，对MABC的治疗有一定的指导意义。本文的在线版本（10.1186/s13046-018-0762-y）包含补充材料，可供授权用户使用。
The most striking feature of molecular apocrine breast cancer (MABC) is the expression of androgen receptor (AR). We report here the mechanism of the AR in regulating the behavior of MABC. The MABC cell line, MDA-MB-453, and the nonMABC cell line, MCF7, were used in this study. The effect of dihydrotestosterone (DHT) and heat shock protein 27 (HSP27) on cell proliferation was quantified using the cell counter kit-8 (CCK8) and clonogenic assays in vitro and by a xenograft tumor model in vivo. The expression of the AR and HSP27 was analyzed using western blot, qPCR, and immunofluorescence assays. Complexes of the AR and HSP27 were detected by co-immunoprecipitation (Co-IP). In MDA-MB-453 cells, DHT promoted cell proliferation and stimulated AR and HSP27 translocation from the cytoplasm to the nucleus, whereas, it inhibited MCF7 cell growth, and only the AR translocated into the nucleus. HSP27 knock-down decreased the proliferative ability of MDA-MB-453 cells, which could be rescued by DHT, while HSP27 and DHT had synergistic effects on MCF7 cells. HSP27 phosphorylation was a prerequisite for AR translocation into the nucleus, especially phosphorylation on serine 82. In addition, DHT stimulated the tumorigenic and metastatic capacities of MDA-MB-453 cells, while HSP27 knock-down decreased the rate of tumor formation and induced apoptosis in cells. The results suggest that HSP27 assists the AR in regulating the malignant behavior of MABC, and these findings might be helpful in the treatment of MABC. The online version of this article (10.1186/s13046-018-0762-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1158/1078-0432.ccr-10-2021
发表时间：
2011-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hu R;Dawood S;Holmes MD;Collins LC;Schnitt SJ;Cole K;Marotti JD;Hankinson SE;Colditz GA;Tamimi RM
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NEBREDA, AR
影响因子：
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影响因子：
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Iggo, R