Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish.
Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish.
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许多核糖体蛋白突变与斑马鱼的生长障碍和肿瘤易感性相关。
DOI：
10.1002/dvdy.21815
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发表时间：
2009-01
影响因子：
2.5
通讯作者：
Lees, Jacqueline A.
中科院分区：
文献类型：
--
作者：
Lai, Kevin;Amsterdam, Adam;Farrington, Sarah;Bronson, Roderick T.;Hopkins, Nancy;Lees, Jacqueline A.
我们已经表征了28条核糖体蛋白（rp）基因杂合突变的斑马鱼品系，并发现其中17条易于发生斑马鱼恶性外周神经鞘瘤（zMPNST）。来自绝大多数肿瘤倾向rp系的杂合子被发现是生长受损的，尽管并非所有生长受损的rp系都是肿瘤倾向的。然而，值得注意的是，zMPNST发生率最高的rp系都显示出生长障碍。此外，来自一个肿瘤倾向rp系的杂合细胞在嵌合体胚胎中被野生型细胞竞争。许多rp基因的杂合性导致的生长障碍表明，在这些细胞系中存在蛋白质翻译的整体缺陷，提高了肿瘤发生前的翻译缺陷预测肿瘤发生的可能性。
We have characterized 28 zebrafish lines with heterozygous mutations in ribosomal protein (rp) genes, and found that 17 of these are prone to develop zebrafish malignant peripheral nerve sheath tumors (zMPNST). Heterozygotes from the vast majority of tumor-prone rp lines were found to be growth-impaired, though not all growth-impaired rp lines were tumor-prone. Significantly, however, the rp lines with the greatest incidence of zMPNSTs all displayed a growth impairment. Furthermore, heterozygous cells from one tumor-prone rp line were out-competed by wild-type cells in chimeric embryos. The growth impairment resulting from heterozygosity for many rp genes suggests that a global defect in protein translation exists in these lines, raising the possibility that a translation defect that precedes tumor development is predictive of tumorigenesis.
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