期刊
ONCOGENE
卷 32, 期 2, 页码 222-233出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.36
关键词
Trop-2; human tumours; cell growth; signalling; oncogene
资金
- Fondazione of the Cassa di Risparmio della Provincia di Chieti
- ABO Foundation [CH01D0081]
- Fondazione compagnia di San Paolo
- Italian Ministry of Health [RicOncol RF-EMR-2006-361866]
- Italian Foundation for Cancer Research (FIRC, Italy)
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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
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