Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish.
Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish.
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DOI：
10.1186/1476-4598-8-40
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发表时间：
2009-06-25
期刊：
影响因子：
37.3
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Ju B;Spitsbergen J;Eden CJ;Taylor MR;Chen W
斑马鱼已成为癌症研究的重要模型。已经通过在斑马鱼中转基因表达人或小鼠癌基因建立了几种癌症模型。由于斑马鱼易于进行高效的转基因，因此它具有巨大的潜力，可用于研究生物体水平上癌基因和途径的相互作用。利用Gal 4VP 16-UAS二元转基因表达方法，我们建立了稳定的表达激活的斑马鱼Smoothened（Smoa 1-EGFP）的EGFP融合蛋白的转基因系。斑马鱼Smoa 1-EGFP本身的表达并没有导致肿瘤的形成，无论是在创始人鱼或后代，然而，共表达的组成型活性的人AKT 1导致几种肿瘤类型，包括梭形细胞肉瘤，横纹肌瘤，眼黑色素瘤，星形细胞瘤，和myoxma。所有肿瘤类型均显示GFP表达和增加的Patched 1水平，表明斑马鱼Smoa 1参与肿瘤发生。免疫荧光研究表明，肿瘤还表达了磷酸化AKT水平升高，表明PI 3 K-AKT通路的激活。这些结果表明，刺猬和AKT通路的共激活促进肿瘤发生，并且二元转基因方法是研究斑马鱼中癌基因和致癌通路相互作用的有用工具。
The zebrafish has become an important model for cancer research. Several cancer models have been established by transgenic expression of human or mouse oncogenes in zebrafish. Since it is amenable to efficient transgenesis, zebrafish have immense potential to be used for studying interaction of oncogenes and pathways at the organismal level. Using the Gal4VP16-UAS binary transgenic expression approach, we established stable transgenic lines expressing an EGFP fusion protein of an activated zebrafish Smoothened (Smoa1-EGFP). Expression of the zebrafish Smoa1-EGFP itself did not lead to tumor formation either in founder fish or subsequent generations, however, co-expressing a constitutively active human AKT1 resulted in several tumor types, including spindle cell sarcoma, rhabdomyoma, ocular melanoma, astrocytoma, and myoxma. All tumor types showed GFP expression and increased Patched 1 levels, suggesting involvement of zebrafish Smoa1 in tumorigenesis. Immunofluorescence studies showed that tumors also expressed elevated levels of phosphorylated AKT, indicating activation of the PI3K-AKT pathway. These results suggest that co-activation of the hedgehog and AKT pathways promote tumorigenesis, and that the binary transgenic approach is a useful tool for studying interaction of oncogenes and oncogenic pathways in zebrafish.
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影响因子：
2.7
作者：
Davison, Jon M.;Akitake, Courtney M.;Parsons, Michael J.
通讯作者：
Parsons, Michael J.
影响因子：
11.2
作者：
Segrelles, Carmen;Lu, Jerry;DiGiovanni, John
通讯作者：
DiGiovanni, John
影响因子：
8
作者：
Wicking, C;Smyth, I;Bale, A
通讯作者：
Bale, A
DOI：
10.1073/pnas.0504337103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Riobó, NA;Lu, K;Emerson, CP
通讯作者：
Emerson, CP
影响因子：
82.9
作者：
Fan, HR;Oro, AE;Khavari, PA
通讯作者：
Khavari, PA