Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.

TitleRadiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
Publication TypeJournal Article
Year of Publication2011
AuthorsNguyen DH, Oketch-Rabah HA, Illa-Bochaca I, Geyer FC, Reis-Filho JS, Mao J-H, Ravani SA, Zavadil J, Borowsky AD, Jerry JD, Dunphy KA, Seo JH, Haslam S, Medina D, Barcellos-Hoff MH
JournalCancer cell
Volume19
Issue5
Pagination640-51
Date Published2011 May 17
ISSN1878-3686
KeywordsAnimals, Breast Neoplasms, Cell Transformation, Neoplastic, Dose-Response Relationship, Radiation, Epithelial Cells, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Mammary Glands, Animal, Mice, Mice, Inbred BALB C, Mice, Knockout, Neoplasms, Radiation-Induced, Radiation Chimera, Reaction Time, Receptors, Estrogen, Time Factors, Transforming Growth Factor beta1, Tumor Burden, Tumor Microenvironment, Tumor Suppressor Protein p53, Whole-Body Irradiation
AbstractTissue 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.
DOI10.1016/j.ccr.2011.03.011
Alternate JournalCancer Cell
PubMed ID21575864