Title |
Radiation Acts on the Microenvironment to Affect Breast Carcinogenesis by Distinct Mechanisms that Decrease Cancer Latency and Affect Tumor Type
|
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Published in |
Cancer Cell, May 2011
|
DOI | 10.1016/j.ccr.2011.03.011 |
Pubmed ID | |
Authors |
David H. Nguyen, Hellen A. Oketch-Rabah, Irineu Illa-Bochaca, Felipe C. Geyer, Jorge S. Reis-Filho, Jian-Hua Mao, Shraddha A. Ravani, Jiri Zavadil, Alexander D. Borowsky, D. Joseph Jerry, Karen A. Dunphy, Jae Hong Seo, Sandra Haslam, Daniel Medina, Mary Helen Barcellos-Hoff |
Abstract |
Tissue microenvironment is an important determinant of carcinogenesis. We demonstrate that ionizing radiation, a known carcinogen, affects cancer frequency and characteristics by acting on the microenvironment. Using a mammary chimera model in which an irradiated host is transplanted with oncogenic Trp53 null epithelium, we show accelerated development of aggressive tumors whose molecular signatures were distinct from tumors arising in nonirradiated hosts. Molecular and genetic approaches show that TGFβ mediated tumor acceleration. Tumor molecular signatures implicated TGFβ, and genetically reducing TGFβ abrogated the effect on latency. Surprisingly, tumors from irradiated hosts were predominantly estrogen receptor negative. This effect was TGFβ independent and linked to mammary stem cell activity. Thus, the irradiated microenvironment affects latency and clinically relevant features of cancer through distinct and unexpected mechanisms. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 67 | 35% |
Austria | 2 | 1% |
China | 2 | 1% |
Australia | 1 | <1% |
Germany | 1 | <1% |
Korea, Republic of | 1 | <1% |
United States | 1 | <1% |
Unknown | 118 | 61% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 189 | 98% |
Scientists | 2 | 1% |
Practitioners (doctors, other healthcare professionals) | 1 | <1% |
Unknown | 1 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 5 | 4% |
Japan | 2 | 2% |
South Africa | 1 | <1% |
United Kingdom | 1 | <1% |
Canada | 1 | <1% |
Netherlands | 1 | <1% |
Singapore | 1 | <1% |
Italy | 1 | <1% |
New Zealand | 1 | <1% |
Other | 1 | <1% |
Unknown | 113 | 88% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 37 | 29% |
Student > Ph. D. Student | 29 | 23% |
Professor > Associate Professor | 12 | 9% |
Student > Master | 11 | 9% |
Student > Bachelor | 8 | 6% |
Other | 18 | 14% |
Unknown | 13 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 51 | 40% |
Biochemistry, Genetics and Molecular Biology | 23 | 18% |
Medicine and Dentistry | 15 | 12% |
Engineering | 7 | 5% |
Physics and Astronomy | 4 | 3% |
Other | 11 | 9% |
Unknown | 17 | 13% |