Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma

Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma
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DOI:
10.1158/0008-5472.can-04-2247
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发表时间:
2004-12-01
期刊:
影响因子:
11.2
通讯作者:
Mercurio, AM
Mercurio, AM
中科院分区:
医学1区
文献类型:
--
作者:
Simpson, KJ;Dugan, AS;Mercurio, AM

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虽然RhoA和RhoC蛋白包含Rho GTdR家族的一个重要子集,该家族与浸润性乳腺癌有关,但将特定功能归因于这些个体成员一直很困难。我们已经使用了一种稳定的逆转录病毒RNA干扰方法来产生侵袭性乳腺癌细胞(SUM-159细胞),缺乏RhoA或RhoC表达。对这些细胞的分析使我们能够推断RhoA阻碍和RhoC刺激侵袭。出乎意料的是,该分析还揭示了RhoA和RhoC之间在其表达和激活水平上的补偿关系,以及RhoA和Rac 1激活之间的相互关系。
Although the RhoA and RhoC proteins comprise an important subset of the Rho GTPase family that have been implicated in invasive breast carcinomas, attributing specific functions to these individual members has been difficult. We have used a stable retroviral RNA interference approach to generate invasive breast carcinoma cells (SUM-159 cells) that lack either RhoA or RhoC expression. Analysis of these cells enabled us to deduce that RhoA impedes and RhoC stimulates invasion. Unexpectedly, this analysis also revealed a compensatory relationship between RhoA and RhoC at the level of both their expression and activation, and a reciprocal relationship between RhoA and Rac1 activation.