Lymphoid and mesenchymal tumors in transgenic mice expressing the v-fps protein-tyrosine kinase

Lymphoid and mesenchymal tumors in transgenic mice expressing the v-fps protein-tyrosine kinase
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表达 v-fps 蛋白酪氨酸激酶的转基因小鼠的淋巴和间质肿瘤

DOI:
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发表时间:
1989
影响因子:
5.3
通讯作者:
T. Pawson
T. Pawson
中科院分区:
生物学2区
文献类型:
--
作者:
S. Yee;D. Mock;P. Greer;V. Maltby;J. Rossant;A. Bernstein;T. Pawson

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Src、abl和fps/fes是编码非受体蛋白酪氨酸激酶的基因家族的原型。通过将福建肉瘤病毒gag-fps编码序列导入小鼠种系,研究了v-fps蛋白酪氨酸激酶的致瘤潜能。在5‘人β -珠蛋白启动子(GF)或5’和3' β -珠蛋白调控序列(GEF)的转录控制下,携带v-fps的转基因小鼠能够存活。出乎意料的是,GF和GEF转基因均在多种组织中表达,并诱导了一系列良性和恶性肿瘤。这些肿瘤包括淋巴瘤、胸腺瘤、纤维肉瘤、血管肉瘤、血管瘤和神经纤维肉瘤,潜伏期为2至12个月,发病频率各不相同。根据t细胞受体β或免疫球蛋白基因的重排判断,大多数淋巴样肿瘤似乎是t细胞起源的单克隆肿瘤。一些表达v-fps致癌基因的组织,如心脏、脑、肺和睾丸,没有发生恶性肿瘤。因此,v-fps蛋白酪氨酸激酶在淋巴细胞和间充质细胞中具有广泛但并非无限制的致癌活性。肿瘤表型的不完全外显性和淋巴样肿瘤的单克隆表明,除了P130gag-fps蛋白酪氨酸激酶的表达外,v-fps小鼠的肿瘤形成还需要遗传或表观遗传事件。
src, abl, and fps/fes are prototypes for a family of genes encoding nonreceptor protein-tyrosine kinases. The oncogenic potential of the v-fps protein-tyrosine kinase was investigated by introduction of the gag-fps coding sequence of Fujinami sarcoma virus into the mouse germ line. Transgenic mice with v-fps under the transcriptional control of a 5' human beta-globin promoter (GF) or with both 5' and 3' beta-globin regulatory sequences (GEF) were viable. Unexpectedly, both GF and GEF transgenes were expressed in a wide variety of tissues and induced a spectrum of benign and malignant tumors. These tumors, which included lymphomas, thymomas, fibrosarcomas, angiosarcomas, hemangiomas, and neurofibrosarcomas, developed with various frequencies after latent periods of 2 to 12 months. The majority of lymphoid neoplasms appeared to be of T-cell origin and were monoclonal, as judged by rearrangements of the T-cell receptor beta or immunoglobulin genes. Some tissues that expressed the v-fps oncogene, such as heart, brain, lung, and testes, developed no malignant tumors. The v-fps protein-tyrosine kinase therefore has a broad but not unrestricted range of oncogenic activity in cells of lymphoid and mesenchymal origin. The incomplete penetrance of the neoplastic phenotype and the monoclonality of lymphoid tumors suggest that tumor formation in v-fps mice requires genetic or epigenetic events in addition to expression of the P130gag-fps protein-tyrosine kinase.
DOI: 10.1126/science.6538699
发表时间: 1984-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
SLAMON, DJ;DEKERNION, JB;CLINE, MJ
通讯作者: CLINE, MJ
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DOI: 10.1073/pnas.83.16.6053
发表时间: 1986
影响因子: 11.1
作者:
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通讯作者: Robinson,HL
DOI: 10.1126/science.2964082
发表时间: 1988-02-26
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: FIELD, LJ