Title |
Pten in stromal fibroblasts suppresses mammary epithelial tumours
|
---|---|
Published in |
Nature, October 2009
|
DOI | 10.1038/nature08486 |
Pubmed ID | |
Authors |
Anthony J. Trimboli, Carmen Z. Cantemir-Stone, Fu Li, Julie A. Wallace, Anand Merchant, Nicholas Creasap, John C. Thompson, Enrico Caserta, Hui Wang, Jean-Leon Chong, Shan Naidu, Guo Wei, Sudarshana M. Sharma, Julie A. Stephens, Soledad A. Fernandez, Metin N. Gurcan, Michael B. Weinstein, Sanford H. Barsky, Lisa Yee, Thomas J. Rosol, Paul C. Stromberg, Michael L. Robinson, Francois Pepin, Michael Hallett, Morag Park, Michael C. Ostrowski, Gustavo Leone |
Abstract |
The tumour stroma is believed to contribute to some of the most malignant characteristics of epithelial tumours. However, signalling between stromal and tumour cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumours. This was associated with the massive remodelling of the extracellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumours ameliorated disruption of the tumour microenvironment and was sufficient to decrease tumour growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumour stroma of patients with breast cancer. These findings identify the Pten-Ets2 axis as a critical stroma-specific signalling pathway that suppresses mammary epithelial tumours. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Canada | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 11 | 2% |
United Kingdom | 6 | 1% |
Switzerland | 4 | <1% |
Netherlands | 2 | <1% |
France | 2 | <1% |
Canada | 2 | <1% |
Germany | 2 | <1% |
India | 2 | <1% |
Austria | 1 | <1% |
Other | 8 | 2% |
Unknown | 412 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 132 | 29% |
Researcher | 101 | 22% |
Professor > Associate Professor | 41 | 9% |
Student > Master | 35 | 8% |
Professor | 26 | 6% |
Other | 76 | 17% |
Unknown | 41 | 9% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 199 | 44% |
Biochemistry, Genetics and Molecular Biology | 80 | 18% |
Medicine and Dentistry | 68 | 15% |
Chemistry | 10 | 2% |
Immunology and Microbiology | 7 | 2% |
Other | 40 | 9% |
Unknown | 48 | 11% |