Transforming growth factor (TGF)-β in conjunction with H-ras activation promotes malignant progression of MCF10A breast epithelial cells
Transforming growth factor (TGF)-β in conjunction with H-ras activation promotes malignant progression of MCF10A breast epithelial cells
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DOI：
10.1016/j.cyto.2004.10.001
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发表时间：
2005-01-21
期刊：
影响因子：
3.8
通讯作者：
Moon, A
中科院分区：
文献类型：
--
作者：
Kim, ES;Kim, MS;Moon, A
为了研究转化生长因子(TGF)- β和致瘤性H-ras信号转导通路在乳腺上皮细胞恶性进展中的相互作用，我们在本研究中研究了TGF- β信号转导通路在H-ras转化的MCF10A人乳腺上皮细胞侵袭性和迁移性中的作用。本研究表明，tgf - β处理显著增强了H-ras MCF10A细胞的侵袭和迁移。tgf - β刺激h -ras介导的p38 MAPK和ERK-1/2的激活。tgf - β通过转录激活增加基质金属蛋白酶(MMP)-2的表达，而tgf - β刺激的MMP-9不发生转录水平的上调。tgf - β诱导的细胞迁移、侵袭和MMP-2/-9上调需要激活p38 MAPK通路，这表明p38 MAPK信号在tgf - β促进的h -ras活化细胞的肿瘤进展中起关键作用。ERKs信号对于tgf - β增强的侵袭和迁移表型也至关重要，但MMP-2/-9的上调并不依赖于ERKs活性。综上所述，我们发现tgf - β促进了h -ras介导的细胞迁移和侵袭性表型，其中p38 MAPK和ERKs信号通路参与其中。我们的发现揭示了H-ras和tgf - β信号通路如何在MCF10A人乳腺细胞中相互作用，这可能为tgf - β与活化的H-ras协同促进乳腺癌恶性进展的分子机制提供了见解。(C) 2004 Elsevier Ltd.版权所有。
To address how transforming growth factor (TGF)-beta and oncogenic H-ras signal transduction pathways interact with each other in the malignant progression of breast epithelial cells, we investigated the role of TGF-beta signaling pathway in invasive and migrative properties of H-ras-transformed MCF10A human breast epithelial cells in this study. Here we show that TGF-beta treatment significantly enhanced invasion and migration of H-ras MCF10A cells. H-ras-mediated activation of p38 MAPK and ERK-1/2 was stimulated by TGF-beta. TGF-beta increased expression of matrix metalloproteinase (MMP)-2 through transcriptional activation while TGF-beta-stimulated MMP-9 up-regulation did not occur at transcription level. Activation of p38 MAPK pathway was required for TGF-beta-induced cell migration, invasion and MMP-2/-9 up-regulation, indicating a critical role of p38 MAPK signaling in TGF-beta-promoted tumor progression of H-ras-activated cells. ERKs signaling was also crucial for TGF-beta-enhanced invasive and migrative phenotypes but the up-regulation of MMP-2/-9 was not dependent on ERKs activity. Taken together, we show that TGF-beta promotes H-ras-mediated cell migration and invasive phenotypes in which p38 MAPK and ERKs signaling pathways are involved. Our findings revealing how H-ras and TGF-beta signal pathways interact with each other in MCF10A human breast cells may provide an insight into molecular mechanisms for contribution of TGF-beta to a malignant progression of breast cancer in collaboration with activated H-ras. (C) 2004 Elsevier Ltd. All rights reserved.