Upregulation of Trop-2 quantitatively stimulates human cancer growth
Upregulation of Trop-2 quantitatively stimulates human cancer growth
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DOI：
10.1038/onc.2012.36
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发表时间：
2013-01-10
期刊：
影响因子：
8
通讯作者：
Alberti, S.
中科院分区：
文献类型：
--
作者：
Trerotola, M.;Cantanelli, P.;Alberti, S.
Trop-2是与实验系统中的转化细胞生长相关的钙信号转导子。然而，它在人类癌症中的作用基本上仍然未知。在这项研究中，我们分析了Trop-2在正常人体组织中的mRNA和蛋白质水平的表达。然后，我们系统地比较了Trop-2 mRNA和蛋白质水平在肿瘤与其组织的起源。我们发现Trop-2表达在肿瘤中总是上调，而不管正常组织中的基线表达，这表明了相应的选择性优势。因此，我们研究了Trop-2上调对肿瘤生长的结果。野生型Trop-2的过表达被证明是必要的，并且足以在细胞类型和物种之间以广泛不变的方式驱动癌症生长。显示Trop-2的上调定量地刺激肿瘤生长，与体内表达水平成比例，并且肿瘤细胞生长通过Trop-2表达的体细胞敲低而消除。另一方面，我们没有发现与肿瘤相关的TROP 2突变的证据，也没有发现TROP 2本身诱导致癌转化的证据。我们的数据支持一个模型，其中野生型Trop-2的高于基线的表达是人类癌症生长的关键驱动因素。Oncogene（2013）32，222-233; doi：10.1038/onc.2012.36; 2012年2月20日在线发表
Trop-2 is a calcium signal transducer that is associated with transformed cell growth in experimental systems. However, its role in human cancer remains essentially unknown. In this study, we profiled Trop-2 expression in normal human tissues at the mRNA and protein levels. We then systematically compared Trop-2 mRNA and protein levels in tumours with their tissues of origin. We find that Trop-2 expression is invariably upregulated in tumours, regardless of baseline expression in normal tissues, which suggests a corresponding selective advantage. Thus, we investigated the outcome of Trop-2 upregulation on tumour growth. Overexpression of wild-type Trop-2 was shown to be necessary and sufficient to drive cancer growth in a widely invariant manner across cell type and species. Upregulation of Trop-2 was shown to quantitatively stimulate tumour growth, as proportional to expression levels in vivo, and tumour cell growth was abrogated by somatic knockdown of Trop-2 expression. On the other hand, we found no evidence of tumour-associated TROP2 mutations, nor of TROP2 induction of oncogenic transformation per se. Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth. Oncogene (2013) 32, 222-233; doi:10.1038/onc.2012.36; published online 20 February 2012