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. 2013 Jan 10;32(2):222-33.
doi: 10.1038/onc.2012.36. Epub 2012 Feb 20.

Upregulation of Trop-2 quantitatively stimulates human cancer growth

M Trerotola  1 , P Cantanelli, E Guerra, R Tripaldi, A L Aloisi, V Bonasera, R Lattanzio, R de Lange, U H Weidle, M Piantelli, S Alberti
Affiliations

Upregulation of Trop-2 quantitatively stimulates human cancer growth

M Trerotola et al. Oncogene. .

Abstract

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.

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