S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation.
S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation.
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S100A7-下调抑制了乳腺癌细胞中表皮生长因子诱导的信号传导，并阻止破骨细胞的形成。
DOI：
10.1371/journal.pone.0001741
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发表时间：
2008-03-05
期刊：
影响因子：
3.7
通讯作者：
Ganju, Ramesh K.
中科院分区：
文献类型：
--
作者：
Paruchuri, Vikram;Prasad, Anil;McHugh, Kevin;Bhat, Hari K.;Polyak, Kornelia;Ganju, Ramesh K.
S100 A7是一种小的钙结合蛋白，已被证明在银屑病皮肤病变以及皮肤、肺和乳腺的鳞状细胞肿瘤中差异表达。尽管其表达与HER+高级别肿瘤和高进展风险相关，但这些S100 A7介导的致瘤作用的分子机制尚不清楚。在这里，我们首次发现表皮生长因子（EGF）诱导MCF-7和MDA-MB-468细胞系中S100 A7的表达。我们还观察到在shRNA下调的MDA-MB-468细胞系中EGF引导的迁移减少。此外，我们的信号转导研究表明，EGF诱导同时EGF受体磷酸化在Tyr 1173和HER 2磷酸化在Tyr 1248在S100 A7下调的细胞系相比，载体转染的控制。此外，在这些下调的细胞系中观察到Src在酪氨酸416处和p-SHP 2在酪氨酸542处的磷酸化减少。进一步的研究显示，基于基质胶塞测定，S100 A7下调的细胞在体内具有减少的血管生成。我们的研究结果还表明，在涉及SCID小鼠的胫骨内骨注射模型中，肿瘤诱导的骨吸收减少。与载体对照相比，S100 A7下调的细胞具有减少的破骨细胞数量和大小，并且这种减少与体外细胞培养物中IL-8表达的变化相关。这是关于S100 A7在乳腺癌细胞中EGF诱导的信号传导和破骨细胞形成中的作用的新报告。
S100A7 is a small calcium binding protein, which has been shown to be differentially expressed in psoriatic skin lesions, as well as in squamous cell tumors of the skin, lung and breast. Although its expression has been correlated to HER+ high-grade tumors and to a high risk of progression, the molecular mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here, we showed for the first time that epidermal growth factor (EGF) induces S100A7 expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines. Furthermore, our signaling studies revealed that EGF induced simultaneous EGF receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7-downregulated cell lines as compared to the vector-transfected controls. In addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine 542 was observed in these downregulated cell lines. Further studies revealed that S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel plug assays. Our results also showed decreased tumor-induced osteoclastic resorption in an intra-tibial bone injection model involving SCID mice. S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation.
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影响因子：
3.9
作者：
Angelucci, A;Gravina, GL;Bologna, M
通讯作者：
Bologna, M
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45.3
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DiGiovanna, MP;Stern, DF;Thor, AD
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Price, JE
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11.2
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6.4
作者：
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Singer, CF