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【Cell】致癌性BRAF 通过分泌性蛋白IGFBP7 介导的通
Expression of an oncogene in a primary cell can, paradoxically, block proliferation by inducing senescence or apoptosis through pathways that remain to be elucidated. Here we perform genome-wide RNA-interference screening to identify 17 genes required for an activated BRAF oncogene (BRAFV600E) to block proliferation of human primary fibroblasts and melanocytes. Surprisingly, we find a secreted protein, IGFBP7, has a central role in BRAFV600E-mediated senescence and apoptosis. Expression of BRAFV600E in primary cells leads to synthesis and secretion of IGFBP7, which acts through autocrine/paracrine pathways to inhibit BRAF-MEK-ERK signaling and induce senescence and apoptosis. Apoptosis results from IGFBP7-mediated upregulation of BNIP3L, a proapoptotic BCL2 family protein. Recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAFV600E-positive human melanoma cell lines, and systemically administered rIGFBP7 markedly suppresses growth of BRAFV600E-positive tumors in xenografted mice. Immunohistochemical analysis of human skin, nevi, and melanoma samples implicates loss of IGFBP7 expression as a critical step in melanoma genesis.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSN-4RSJ9JW-9&_user=4708741&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=4708741&md5=bd67a81b9690d622a6c815e704f23077 本人认领本文翻译，若48小时内未完成，请战友认领 Oncogenic BRAF Induces Senescence and Apoptosis through Pathways Mediated by the Secreted Protein IGFBP7
BRAF癌基因通过分泌蛋白IGFBP7途径诱导细胞的衰老与凋亡
Expression of an oncogene in a primary cell can, paradoxically, block proliferation by inducing senescence or apoptosis through pathways that remain to be elucidated.
初始细胞的癌基因的表达往往会通过诱导细胞凋亡、衰老来阻止细胞的增值的，而其实现上述功能的具体途径仍有待澄清。
Here we perform genome-wide RNA-interference screening to identify 17 genes required for an activated BRAF oncogene (BRAFV600E) to block proliferation of human primary fibroblasts and melanocytes.
在这里，我们进行全基因组的RNA干涉筛选来确定：实现激活BRAF基因（BRAFV600E）进而阻止人类初级成纤维细胞和黑素细胞增值这一功能所需的17个基因。
Surprisingly, we find a secreted protein, IGFBP7, has a central role in BRAFV600E-mediated senescence and apoptosis.
令人惊讶的是，我们发现一个分泌蛋白， IGFBP7 在BRAFV600E介导的衰老和凋亡中发挥核心作用。
Expression of BRAFV600E in primary cells leads to synthesis and secretion of IGFBP7, which acts through autocrine/paracrine pathways to inhibit BRAF-MEK-ERK signaling and induce senescence and apoptosis.
初始细胞中表达BRAFV600会导致细胞合成和分泌IGFBP7 ，进而通过自/旁分泌途径抑制BRAF-MEK-ERK的信号传导，实现诱导细胞衰老和凋亡。
Apoptosis results from IGFBP7-mediated upregulation of BNIP3L, a proapoptotic BCL2 family protein.
IGFBP7介导BNIP3L（BCL2凋亡蛋白质家族中一员）的上调，导致细胞凋亡。
Recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAFV600E-positive human melanoma cell lines, and systemically administered rIGFBP7 markedly suppresses growth of BRAFV600E-positive tumors in xenografted mice.
重组IGFBP7（rIGFBP7）诱导BRAFV600E阳性的人黑色素瘤细胞系凋亡，并系统接受rIGFBP7明显抑制BRAFV600E阳性肿瘤在移植小鼠上的生长。
Immunohistochemical analysis of human skin, nevi, and melanoma samples implicates loss of IGFBP7 expression as a critical step in melanoma genesis.
对于人体皮肤、痣和黑色素瘤样本免疫组织化学分析，均提示：IGFBP7表达的缺失为黑色素瘤形成的一个关键步骤。 编译：
BRAF癌基因通过分泌蛋白IGFBP7途径诱导细胞的衰老与凋亡
初始细胞的癌基因的表达往往会通过诱导细胞凋亡、衰老来阻止细胞的增值的，而其实现上述功能的具体途径仍有待澄清。
在这里，我们进行全基因组的RNA干涉筛选来确定：实现激活BRAF基因（BRAFV600E）进而阻止人类初级成纤维细胞和黑素细胞增值这一功能所需的17个基因。
令人惊讶的是，我们发现：分泌蛋白（IGFBP7 ）在BRAFV600E介导的衰老和凋亡中发挥核心作用。
初始细胞中表达BRAFV600会导致细胞合成和分泌IGFBP7 ，进而通过自/旁分泌途径抑制BRAF-MEK-ERK的信号传导，实现诱导细胞衰老和凋亡。
IGFBP7介导BNIP3L（BCL2凋亡蛋白质家族中一员）的上调，导致细胞凋亡。
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作者:admin@医学,生命科学 2011-05-29 05:11
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