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Pten in stromal fibroblasts suppresses mammary epithelial tumours

Overview of attention for article published in Nature, October 2009
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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.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 452 Mendeley readers of this research output. Click here to see the associated Mendeley record.

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%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 September 2012.
All research outputs
#13,862,653
of 22,660,862 outputs
Outputs from Nature
#82,502
of 90,600 outputs
Outputs of similar age
#76,049
of 93,180 outputs
Outputs of similar age from Nature
#464
of 518 outputs
Altmetric has tracked 22,660,862 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
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