The Ras signaling pathway in mammary tumorigenesis and metastasis
The Ras signaling pathway in mammary tumorigenesis and metastasis
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DOI：
10.1023/a:1009572700317
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发表时间：
2001-01-01
影响因子：
2.5
通讯作者：
Daly, RJ
中科院分区：
文献类型：
--
作者：
Malaney, S;Daly, RJ
GTP 酶的 Ras 超家族充当重要的调节开关，协调细胞外刺激与细胞内信号传导途径的激活和适当的生物反应。该超家族的 Ras 分支包括 H-、K- 和 N-Ras，它们通常在特定的人类癌症中发生突变，但值得注意的是在乳腺癌中不会发生突变。相反，在乳腺癌中，由于与生长因子受体或在这种疾病中通常过度表达的其他酪氨酸激酶的偶联增加，或者调节因子、Ras蛋白本身或下游效应子的表达增加，涉及这些GTP酶的信号传导途径可能会上调。利用体外和体内模型的功能研究表明，Ras 信号传导可以调节与乳腺癌进展相关的多种终点，包括锚定依赖性和独立生长、肿瘤发生、类固醇敏感性和侵袭。最后，对 Ras 超家族的处理和信号传导机制的分析确定了治疗干预的潜在靶标。
The Ras superfamily of GTPases act as important regulatory switches to co-ordinate extracellular stimuli with activation of intracellular signaling pathways and appropriate biological responses. The Ras branch of this superfamily includes H-, K- and N-Ras, which are commonly mutated in particular human cancers, but notably not in those of the breast. Instead, in breast cancer the signaling pathways involving these GTPases may be upregulated due to increased coupling to growth factor receptors or other tyrosine kinases commonly overexpressed in this disease, or increased expression of regulators, the Ras protein itself, or downstream effecters. Functional studies utilizing both in vitro and in vivo models demonstrate that Ras signaling can regulate a variety of endpoints relevant to breast cancer progression, including anchorage dependent and independent growth, tumorigenesis, steroid sensitivity and invasion. Finally, analysis of the processing and signaling mechanisms of the Ras superfamily has identified potential targets for therapeutic intervention.