BMP7 influences proliferation, migration, and invasion of breast cancer cells
BMP7 influences proliferation, migration, and invasion of breast cancer cells
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DOI：
10.1016/j.canlet.2008.09.028
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发表时间：
2009-03-08
期刊：
影响因子：
9.7
通讯作者：
Kallioniemi, Anne
中科院分区：
文献类型：
--
作者：
Alarmo, Emma-Leena;Parssinen, Jenita;Kallioniemi, Anne
骨形态发生蛋白7 （Bone morphogenetic protein 7, BMP7）是一种信号分子，最初是基于其形成骨骼的能力而被发现的。它在发育过程中是必不可少的，最近也与癌症发病有关。我们最近发现BMP7在乳腺癌中过度表达，并且这种增加的表达与早期骨转移形成有关。在本研究中，我们探讨了BMP7功能对乳腺癌细胞表型的可能贡献。我们采用了一种双向方法，在3个内源性高表达的细胞系中使用RNA干扰使BMP7沉默，或者相反，将外源性BMP7添加到5个低表达或不表达BMP7的细胞系的生长培养基中。这些操作导致不同的细胞系特异性表型反应。BMP7处理增加了两种细胞系（BT-474, MDA-MB-231）的细胞生长，而BMP7处理导致四种细胞系（HCC1954, MDA-MB-361， T-47D和ZR-75-30）的细胞生长减少。生长变化是由于不同的机制，因为BMP7沉默导致BT-474细胞通过G1阻滞导致生长抑制，而BMP7处理保护MDA-MB-231细胞免于凋亡。此外，BMP7刺激通过诱导细胞迁移增加2.3倍和细胞侵袭增加3.9倍来改变MDA-MB-231表型。综上所述，BMP7可以促进和抑制乳腺癌细胞系细胞的生长，在合适的环境下，还可以显著诱导乳腺癌细胞的迁移和侵袭。2008爱思唯尔爱尔兰有限公司版权所有。
Bone morphogenetic protein 7 (BMP7) is a signaling molecule originally identified based on its ability to form bone. It is essential during development, and more recently has also been implicated in cancer pathogenesis. We have recently shown that BMP7 is overexpressed in breast cancer, and that this increased expression is associated with early bone metastasis formation. In the present study, we explored the possible contribution of BMP7 function to the breast cancer cell phenotype. A two-way approach was applied in which BMP7 was silenced using RNA interference in three cell lines with high endogenous expression or, conversely, exogenous BMP7 was added to the growth medium of five cell lines with low or no BMP7 expression. These manipulations led to diverse cell line-specific phenotypic responses. BMP7 manipulation increased cell growth in two cell lines (BT-474, MDA-MB-231), and BMP7 treatment led to reduced growth in four cell lines (HCC1954, MDA-MB-361, T-47D, and ZR-75-30). Growth changes were due to distinct mechanisms since BMP7 silencing led to growth inhibition via G1 arrest in BT-474 cells, whereas BMP7 treatment protected MDA-MB-231 cells from apoptosis. Furthermore, BMP7 stimulation altered the MDA-MB-231 phenotype by inducing a distinct 2.3-fold increase in cell migration and an even more dramatic 3.9-fold increase in cell invasion. In conclusion, BMP7 can promote and inhibit cell growth in breast cancer cell lines and, in a suitable environment, can also considerably induce breast cancer cell migration and invasion. (C) 2008 Elsevier Ireland Ltd. All rights reserved.