Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer.

Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer.
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自发性猫乳腺癌是HER2过表达的人类乳腺癌预后不良的模型。

DOI:
10.1158/0008-5472.907.65.3
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发表时间:
2005
期刊:
影响因子:
11.2
通讯作者:
M. F. Di Renzo
M. F. Di Renzo
中科院分区:
医学1区
文献类型:
--
作者:
R. De Maria;M. Olivero;S. Iussich;M. Nakaichi;Tomoaki Murata;B. Biolatti;M. F. Di Renzo

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伴侣动物自发性肿瘤是人类癌症的合适模型,主要是因为动物群体和肿瘤都是遗传异质性的。猫乳腺癌(FMC)是一种高度侵袭性的,主要是激素受体阴性的癌症,已被提出作为预后不良的人类乳腺癌的模型。我们已经鉴定并研究了HER 2基因的猫科直系同源物,该基因是人类癌症的重要预后标志物和治疗靶点。猫HER 2(f-HER 2)基因激酶结构域与人HER 2激酶有92%的相似性。使用定量逆转录-PCR,在3/3个FMC细胞系、1/4个乳腺腺瘤和6/11个FMC样品中发现F-HER 2特异性mRNA增加3- 18倍。Western blot显示抗人HER 2抗体识别与人p185 HER 2共迁移的蛋白。相同的抗体对36份FMC存档样本中的13份进行了强染色。这些数据表明,猫HER 2过表达使FMC与HER 2过表达、预后不良的人乳腺癌亚组同源,并可作为测试侵袭性肿瘤治疗创新方法的合适模型。
Companion animal spontaneous tumors are suitable models for human cancer, primarily because both animal population and the tumors are genetically heterogeneous. Feline mammary carcinoma (FMC) is a highly aggressive, mainly hormone receptor-negative cancer, which has been proposed as a model for poor prognosis human breast cancer. We have identified and studied the feline orthologue of the HER2 gene, which is both an important prognostic marker and therapeutic target in human cancer. Feline HER2 (f-HER2) gene kinase domain is 92% similar to the human HER2 kinase. F-HER2-specific mRNA was found 3- to 18-fold increased in 3 of 3 FMC cell lines, in 1 of 4 mammary adenomas and 6 of 11 FMC samples using quantitative reverse transcription-PCR. Western blot showed that an anti-human HER2 antibody recognized a protein comigrating with the human p185HER2 in FMC cell lines. The same antibodies strongly stained 13 of 36 FMC archival samples. These data show that feline HER2 overexpression qualifies FMC as homologous to the subset of HER2 overexpressing, poor prognosis human breast carcinomas and as a suitable model to test innovative approaches to therapy of aggressive tumors.
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DOI: --
发表时间: 1989
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