Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer
Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer
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DOI：
10.1038/sj.onc.1208328
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发表时间：
2005-05-12
期刊：
影响因子：
8
通讯作者：
Germain, D
中科院分区：
文献类型：
--
作者：
Radke, S;Pirkmaier, A;Germain, D
Skp 2是一种F-box蛋白，参与细胞周期蛋白依赖性激酶（Cdk）抑制剂p27的泛素化和随后的降解。据报道，Skp 2在多种癌症类型中过表达，并与不良预后相关。我们已经鉴定了一种新的Skp 2亚型，我们命名为Skp 2B，它与Skp 2的不同之处仅在于C-末端结构域，而不像Skp 2定位于细胞质。在这里，我们使用定量真实的时间RT-PCR描述了Skp 2和Skp 2B在乳腺癌细胞系和原发性乳腺癌中的相对表达。我们发现，Skp 2B mRNA的表达比Skp 2 mRNA在永生化但非转化的乳腺细胞系184 B5中低10倍。然而，Skp 2B与Skp 2一样频繁地过表达，并且在乳腺癌细胞系和原发性癌症中达到比Skp 2更高的水平。此外，我们发现，细胞质染色是常见的原发性乳腺癌。此外，我们发现表达Skp 2B的异种移植物比表达低水平Skp 2B的异种移植物生长得更快，并且这种效应不依赖于p27降解。因此，这些发现表明，Skp 2B过表达也观察到乳腺癌和确定Skp 2B作为一个假定的癌基因。
Skp2 is an F-box protein involved in the ubiquitination and subsequent degradation of the cyclin-dependent kinase (Cdk) inhibitor p27. Skp2 has been reported to be overexpressed in a variety of cancer types and to correlate with poor prognosis. We have identified a novel isoform of Skp2 we named Skp2B, which differs from Skp2 only in the C-terminal domain and unlike Skp2 localizes to the cytoplasm. Here, we describe the relative expression of both Skp2 and Skp2B in breast cancer cell lines and in primary breast cancers using quantitative real time RT-PCR. We show that Skp2B mRNA is expressed 10-fold less than Skp2 mRNA in the immortalized but non-transformed breast cell line, 184B5. However, Skp2B is overexpressed as frequently as Skp2, and to higher levels than Skp2 in breast cancer cell lines and primary cancers. Further, we show that cytoplasmic staining is frequent in primary breast cancers. In addition, we found that xenografts expressing Skp2B grow faster than xenografts expressing low levels of Skp2B, and that this effect is independent of p27 degradation. These findings therefore suggest that Skp2B overexpression is also observed in breast cancers and identify Skp2B as a putative oncogene.