Stat3 modulates heat shock 27kDa protein expression in breast epithelial cells.
Stat3 modulates heat shock 27kDa protein expression in breast epithelial cells.
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DOI：
10.1016/j.bbrc.2003.12.048
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发表时间：
2004-01
影响因子：
3.1
通讯作者：
Hui Song;S. Ethier;Michele L Dziubinski;Jiayuh Lin
中科院分区：
文献类型：
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作者：
Hui Song;S. Ethier;Michele L Dziubinski;Jiayuh Lin
信号转导子和转录激活子3（Stat 3）的组成性激活常在乳腺癌细胞系中检测到，而在正常乳腺上皮细胞中未检测到。Stat 3被归类为癌基因，因为活化的Stat 3可以介导培养细胞中的致癌转化和裸鼠中的肿瘤形成。在这项研究中，我们研究了乳腺细胞中潜在的Stat 3调控基因。在非恶性端粒酶永生化乳腺细胞（TERT）中表达Stat 3-C（一种组成型活性Stat 3形式）后，对细胞裂解物进行二维（2-D）蛋白质凝胶分析。结果表明，Stat 3-C的表达可显著诱导热休克蛋白27（HSP 27）的表达。进一步的分析表明，在TERT乳腺细胞以及MCF-10A和MDA-MB-453乳腺细胞中，Stat 3-C诱导HSP 27丝氨酸残基78的磷酸化。RT-PCR结果证实Stat 3-C可诱导TERT细胞HSP 27 mRNA的表达。在MDA-MB-468人乳腺癌细胞中通过Stat 3短干扰RNA寡核苷酸敲低Stat 3的结果是，HSP 27显著减少，与Stat 3减少一致。此外，我们观察到Stat 3在MDA-MB-468乳腺癌细胞中与HSP 27和HSP 90物理相关。综上所述，我们的研究结果表明，组成性激活Stat 3上调HSP 27，并可能促进HSP 27的丝氨酸残基78的磷酸化。热休克蛋白27的上调可能是Stat 3信号异常诱导细胞恶性肿瘤的机制之一。
The constitutive activation of signal transducer and activator of transcription 3 (Stat3) is frequently detected in breast carcinoma cell lines but not in normal breast epithelial cells. Stat3 has been classified as an oncogene because activated Stat3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. In this study, we investigated potential Stat3 regulated genes in breast cells. Upon expression of Stat3-C, a constitutively active Stat3 form, in nonmalignant telomerase immortalized breast cells (TERT), cell lysate was subjected to 2-dimensional (2-D) protein gel analysis. Our results showed that heat shock 27kDa protein (HSP27) was markedly induced by Stat3-C expression. Further analysis demonstrated that phosphorylation of HSP27 at serine residue 78 was induced by Stat3-C in TERT breast cells as well as in MCF-10A and MDA-MB-453 breast cells. RT-PCR result confirmed that HSP27 mRNA was induced by Stat3-C in TERT cells. As the result of Stat3 knock-down by Stat3 short interfering RNA oligonucleotides in MDA-MB-468 human breast carcinoma cells, HSP27 was markedly reduced consistent with Stat3 reduction. Furthermore, we observed that Stat3 was physically associated with HSP27 and HSP90 in MDA-MB-468 breast carcinoma cells. Taken together, our findings demonstrate that constitutively activated Stat3 up-regulates HSP27 and may facilitate phosphorylation of HSP27 at serine residue 78. The up-regulation of HSP27 may be one of the underlying mechanisms with which aberrant Stat3 signaling induces cell malignancies.