Upregulation of Trop-2 quantitatively stimulates human cancer growth
- 20 February 2012
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 32 (2), 222-233
- https://doi.org/10.1038/onc.2012.36
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.Keywords
This publication has 53 references indexed in Scilit:
- Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathwayMolecular Cancer, 2010
- Primitive origins of prostate cancer: In vivo evidence for prostate‐regenerating cells and prostate cancer‐initiating cellsMolecular Oncology, 2010
- TROP2 expression as prognostic marker for gastric carcinomaJournal of Clinical Pathology, 2008
- High expression of TROP2 correlates with poor prognosis in pancreatic cancerBritish Journal of Cancer, 2008
- Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancersMolecular Cancer Therapeutics, 2008
- TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavityLaboratory Investigation, 2008
- Human TROP-2 is a tumor-associated calcium signal transducerInternational Journal of Cancer, 1998
- Cloning of the gene encoding TROP‐2, a cell‐surface glycoprotein expressed by human carcinomasInternational Journal of Cancer, 1995
- The epithelial/carcinoma antigen EGP‐1, recognized by monoclonal antibody RS7–3G11, is phosphorylated on serine 303International Journal of Cancer, 1995
- Expression of 38-kD Cell-Surface Glycoprotein in Transformed Keratinocyte Cell Lines, Basal Cell Carcinomas, and Epithelial GermsJournal of Investigative Dermatology, 1990