Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer.
Identification of the functional role of peroxiredoxin 6 in the progression of breast cancer.
复制标题
鉴定过氧蛋白6在乳腺癌进展中的功能作用。
DOI：
10.1186/bcr1789
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Shao ZM
中科院分区：
文献类型：
--
作者：
Chang XZ;Li DQ;Hou YF;Wu J;Lu JS;Di GH;Jin W;Ou ZL;Shen ZZ;Shao ZM
乳腺癌转移的分子机制至今仍不清楚。在我们先前的研究中，发现高转移性MDA-MB-435 HM细胞和其亲本对应物MDA-MB-435细胞之间存在过氧化物酶6的差异表达。本研究探讨了Peroxiredoxin 6对人乳腺癌细胞增殖和转移能力的影响及其可能机制。采用RT-PCR、real-time PCR和western blot检测Peroxiredoxin 6在MDA-MB-231 HM高转移细胞中的表达。构建了人过氧化物酶6基因的重组表达质粒，并转染MDA-MB-231和MDA-MB-435细胞。采用细胞计数法、集落形成实验、粘附实验、流式细胞术和体外侵袭实验研究Peroxiredoxin 6对MDA-MB-231和MDA-MB-435细胞增殖和侵袭的影响。miRNA用于下调peroxiredoxin 6的表达。采用RT-PCR、real-time PCR和western blot检测肿瘤侵袭转移相关基因。使用原位异种移植肿瘤模型在无胸腺小鼠中测定由过氧化物氧还蛋白6调节的致瘤性和自发转移能力。证实了MDA-MB-231 HM细胞中过氧化物氧还蛋白6的过表达。Peroxiredoxin 6的上调增强了乳腺癌细胞的体外增殖和侵袭。这种增强与基质金属蛋白酶组织抑制剂（TIMP）-2水平降低和尿激酶型纤溶酶原激活物受体（uPAR）、Ets-1（E26转化特异性-1）、基质金属蛋白酶（MMP）-9和RhoC（ras同源基因家族，成员C）表达水平升高有关。体外RNA干扰实验进一步证实了上述结果。在体内研究中，我们还证明了peroxiredoxin 6转染的乳腺癌细胞比对照细胞生长得更快，并且具有更多的肺转移。相比之下，peroxiredoxin 6敲低乳腺癌细胞生长更慢，肺转移更少。在体内研究中发现了与在体外研究中观察到的peroxiredoxin 6对uPAR、Ets-1、MMP-9、RhoC和TIMP-2表达的作用相似的作用。peroxiredoxin 6的过表达导致人乳腺癌中更具侵袭性的表型和转移潜力，至少部分是通过调节uPAR、Ets-1、MMP-9、RhoC和TIMP-2的表达水平。
The molecular mechanisms involved in breast cancer metastasis still remain unclear to date. In our previous study, differential expression of peroxiredoxin 6 was found between the highly metastatic MDA-MB-435HM cells and their parental counterparts, MDA-MB-435 cells. In this study, we investigated the effects of peroxiredoxin 6 on the proliferation and metastatic potential of human breast cancer cells and their potential mechanism. Expression of peroxiredoxin 6 in the highly metastatic MDA-MB-231HM cells was investigated by RT-PCR, real-time PCR and western blot. A recombinant expression plasmid of the human peroxiredoxin 6 gene was constructed and transfected into MDA-MB-231 and MDA-MB-435 cells. The effects of peroxiredoxin 6 on the proliferation and invasion of MDA-MB-231 and MDA-MB-435 cells were investigated by the Cell Counting Kit-8 method, colony-formation assay, adhesion assay, flow cytometry and invasion assay in vitro. miRNA was used to downregulate the expression of peroxiredoxin 6. Genes related to the invasion and metastasis of cancer were determined by RT-PCR, real-time PCR and western blot. The tumorigenicity and spontaneously metastatic capability regulated by peroxiredoxin 6 were determined using an orthotopic xenograft tumor model in athymic mice. Overexpression of peroxiredoxin 6 in MDA-MB-231HM cells compared with their parental counterparts was confirmed. Upregulation of peroxiredoxin 6 enhanced the in vitro proliferation and invasion of breast cancer cells. The enhancement was associated with decreasing levels of tissue inhibitor of matrix metalloproteinase (TIMP)-2 and increasing levels of the urokinase-type plasminogen activator receptor (uPAR), Ets-1 (E26 transformation-specific-1), matrix metalloproteinase (MMP)-9 and RhoC (ras homolog gene family, member C) expression. The results were further demonstrated by RNA interference experiments in vitro. In an in vivo study, we also demonstrated that peroxiredoxin 6-transfected breast cancer cells grew much faster and had more pulmonary metastases than control cells. By contrast, peroxiredoxin 6 knockdown breast cancer cells grew more slowly and had fewer pulmonary metastases. Effects similar to those of peroxiredoxin 6 on the uPAR, Ets-1, MMP-9, RhoC and TIMP-2 expression observed in in vitro studies were found in the in vivo study. Overexpression of peroxiredoxin 6 leads to a more invasive phenotype and metastatic potential in human breast cancer, at least in part, through regulation of the levels of uPAR, Ets-1, MMP-9, RhoC and TIMP-2 expression.
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影响因子：
3.4
作者：
Li, Da-Qiang;Wang, Lei;Shao, Zhi-Min
通讯作者：
Shao, Zhi-Min
影响因子：
4.8
作者：
Kang, SW;Baines, IC;Rhee, SG
通讯作者：
Rhee, SG
影响因子：
11.2
作者：
Liu, Y;Liu, HL;Zhang, JT
通讯作者：
Zhang, JT
影响因子：
4
作者：
Chang, Xin-Zhong;Wang, Zhan-Min;Shao, Zhi-Min
通讯作者：
Shao, Zhi-Min
影响因子：
5.3
作者：
Wang, XS;Phelan, SA;Paigen, B
通讯作者：
Paigen, B