Title |
Stromal PTEN determines mammary epithelial response to radiotherapy
|
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Published in |
Nature Communications, July 2018
|
DOI | 10.1038/s41467-018-05266-6 |
Pubmed ID | |
Authors |
Gina M. Sizemore, Subhasree Balakrishnan, Katie A. Thies, Anisha M. Hammer, Steven T. Sizemore, Anthony J. Trimboli, Maria C. Cuitiño, Sarah A. Steck, Gary Tozbikian, Raleigh D. Kladney, Neelam Shinde, Manjusri Das, Dongju Park, Sarmila Majumder, Shiva Krishnan, Lianbo Yu, Soledad A. Fernandez, Arnab Chakravarti, Peter G. Shields, Julia R. White, Lisa D. Yee, Thomas J. Rosol, Thomas Ludwig, Morag Park, Gustavo Leone, Michael C. Ostrowski |
Abstract |
The importance of the tumor-associated stroma in cancer progression is clear. However, it remains uncertain whether early events in the stroma are capable of initiating breast tumorigenesis. Here, we show that in the mammary glands of non-tumor bearing mice, stromal-specific phosphatase and tensin homolog (Pten) deletion invokes radiation-induced genomic instability in neighboring epithelium. In these animals, a single dose of whole-body radiation causes focal mammary lobuloalveolar hyperplasia through paracrine epidermal growth factor receptor (EGFR) activation, and EGFR inhibition abrogates these cellular changes. By analyzing human tissue, we discover that stromal PTEN is lost in a subset of normal breast samples obtained from reduction mammoplasty, and is predictive of recurrence in breast cancer patients. Combined, these data indicate that diagnostic or therapeutic chest radiation may predispose patients with decreased stromal PTEN expression to secondary breast cancer, and that prophylactic EGFR inhibition may reduce this risk. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 33% |
United States | 1 | 17% |
Germany | 1 | 17% |
Unknown | 2 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 4 | 67% |
Members of the public | 2 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 42 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 21% |
Researcher | 6 | 14% |
Student > Doctoral Student | 3 | 7% |
Student > Bachelor | 2 | 5% |
Student > Master | 2 | 5% |
Other | 5 | 12% |
Unknown | 15 | 36% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 8 | 19% |
Medicine and Dentistry | 7 | 17% |
Agricultural and Biological Sciences | 3 | 7% |
Chemistry | 2 | 5% |
Linguistics | 1 | 2% |
Other | 6 | 14% |
Unknown | 15 | 36% |