INABILITY OF ROUS-SARCOMA VIRUS TO CAUSE SARCOMAS IN THE AVIAN EMBRYO

INABILITY OF ROUS-SARCOMA VIRUS TO CAUSE SARCOMAS IN THE AVIAN EMBRYO
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DOI:
10.1038/309552a0
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发表时间:
1984-01-01
期刊:
影响因子:
64.8
通讯作者:
BISSELL, MJ
BISSELL, MJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DOLBERG, DS;BISSELL, MJ

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将鲁斯肉瘤病毒(RSV)注射到新孵化的雏鸡的翼网中会导致快速生长的肉瘤,接种后1周内可触及到1;来自鸡胚(CEF)并感染RSV的成纤维细胞的培养迅速转化2。遗传学研究已经确定,单个病毒基因v-src的表达是肿瘤转化所必需的。该基因编码一种名为pp60src的60,000分子量的磷蛋白,它具有使酪氨酸残基上的多肽磷酸化的蛋白激酶活性,并在感染的CEF细胞4中结构性表达。有人认为,转化和可能的肿瘤形成,可能仅仅是这种酪氨酸磷酸化增加的后果。呼吸道合胞病毒在鸡胚胎中的致病性尚不清楚。Murphy和Rous5提出,RSV可能导致了“一些胚胎”的“各种组织”中的肿瘤,但Milford和Duran-Reynals6以及其他几个实验室7、8的后续研究没有发现任何证据表明RSV感染的早期胚胎中存在胚胎内肿瘤。鉴于我们目前对RSV致瘤性的理解,Duran-Reynals的发现,如果是正确的,很难解释。因此,我们重新研究了RSV与鸡胚胎的相互作用,并在此证实了RSV显微注射到第4天的鸡胚胎中是非致瘤和非致畸的。此外,我们发现(1)病毒不仅在胚胎中复制,而且还表达一种活性的rc特异性蛋白激酶;(2)一旦来自感染肢体的细胞被破坏并放置在培养中,它们能够在24小时后表达转化的表型。
The injection of Rous sarcoma virus (RSV) into the wing web of newly hatched chicks causes a rapidly growing sarcomatous tumour which is palpable within 1 week of inoculation1; and cultures of fibroblasts derived from chick embryos (CEF) and infected with RSV become rapidly transformed2. Genetic studies have determined that expression of a single viral gene, designated v-src, is necessary for neoplastic transformation3. This gene codes for a 60,000-molecular weight phosphoprotein termed pp60src, which possesses a protein kinase activity that phosphorylates polypeptides on tyrosine residues and is constitutively expressed in infected CEF cells4. It has been suggested that transformation, and possibly tumorigenesis, may result solely from the consequences of this increase in tyrosine phosphorylations4. The pathogenicity of RSV in chick embryos inovois less clear. Murphy and Rous5suggested that RSV may have caused tumours in “various tissues” of “some embryos”, but the subsequent studies of Milford and Duran-Reynals6, as well as several other laboratories7,8, failed to find any evidence of intraembryonic tumours in RSV-infected early embryos. The findings of Duran-Reynals, if correct, cannot be explained easily in view of our present understanding of RSV tumorigenicity. Thus, we have re-examined the interaction of RSV with the avian embryo and confirm here that RSV is non-tumorigenic and non-teratogenic when microinjected into day 4 chicken embryos. In addition, we found that (1) the virus not only replicates in the embryo, but it also expresses an activesrc-specific protein kinase and (2) once the cells from the infected limbs are disrupted and placed in culture, they are capable of expressing the transformed phenotype after a 24-h delay.