External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator
External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator
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DOI：
10.1073/pnas.202162199
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发表时间：
2002-10-01
影响因子：
11.1
通讯作者：
Uesugi, M
中科院分区：
文献类型：
--
作者：
Asada, S;Choi, Y;Uesugi, M
在大约30%的乳腺肿瘤中发现了Her 2癌蛋白的过度表达，Her 2过度表达的患者通常具有更侵袭性的疾病。在这里，我们表明，Her 2基因的表达可以通过抑制两种癌症相关蛋白，DRIP 130/CRSP 130/Sur-2（Ras连接的人介体复合物亚基）和ESX（上皮限制性转录因子）的相互作用来降低。通过短的细胞渗透性肽破坏相互作用降低了Her 2基因的表达，并特别损害了Her 2过表达乳腺癌细胞的生长和活力。ESX与DRIP 130的关联由ESX中8-aa螺旋的小疏水面介导，这表明通过小有机分子使Her 2基因失能的治疗方法。
Overproduction of the Her2 oncoprotein has been found in approximate to30% of breast tumors, and patients who have Her2 excesses typically have more aggressive disease. Here we show that the expression of the Her2 gene can be decreased by inhibiting the interaction of the two cancer-linked proteins, DRIP130/CRSP130/Sur-2 (a Ras-linked subunit of human mediator complexes) and ESX (an epithelial-restricted transcription factor). Disruption of the interaction by a short cell-permeable peptide reduced the expression of the Her2 gene and specifically impaired the growth and viability of Her2-overexpressing breast cancer cells. The association of ESX with DRIP130 is mediated by a small hydrophobic face of an 8-aa helix in ESX, suggesting a therapeutic approach to incapacitating the Her2 gene by small organic molecules.