Irradiation of Juvenile, but not Adult, Mammary Gland Increases Stem Cell Self‐Renewal and Estrogen Receptor Negative Tumors

@article{Tang2014IrradiationOJ,
  title={Irradiation of Juvenile, but not Adult, Mammary Gland Increases Stem Cell Self‐Renewal and Estrogen Receptor Negative Tumors},
  author={Jonathan Tang and Ignacio Fernandez-Garcia and Sangeetha Vijayakumar and Haydeliz Martinez-Ruis and Irineu Illa-Bochaca and David Nguyen and Jian-Hua Mao and Sylvain V. Costes and Mary Helen Barcellos-Hoff},
  journal={STEM CELLS},
  year={2014},
  volume={32}
}
Children exposed to ionizing radiation have a substantially greater breast cancer risk than adults; the mechanism for this strong age dependence is not known. Here we show that pubertal murine mammary glands exposed to sparsely or densely ionizing radiation exhibit enrichment of mammary stem cell and Notch pathways, increased mammary repopulating activity indicative of more stem cells, and propensity to develop estrogen receptor (ER) negative tumors thought to arise from stem cells. We… 
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42 Citations
Background Citations
21
Methods Citations
4
Results Citations
3

42 Citations

Citation Type

Citation Type

Distinct luminal-type mammary carcinomas arise from orthotopic Trp53-null mammary transplantation of juvenile versus adult mice.
TLDR
The notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer is supported.
Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention
TLDR
Low-dose radiation, particularly densely ionizing exposure of aged mice, promoted more aggressive cancers by suppressing antitumor immunity, indicating the potential of dietary intervention with a nontoxic immunomodulatory agent for cancer prevention.
Mammary Stem Cells and Tumor-Initiating Cells Are More Resistant to Apoptosis and Exhibit Increased DNA Repair Activity in Response to DNA Damage
A TGFβ–miR-182–BRCA1 axis controls the mammary differentiation hierarchy
TLDR
The findings reveal that TGFβ modulation of BRCA1 directs mammary epithelial cell fate and, because stem or progenitor cells are thought to be the cell of origin for aggressive breast cancer subtypes, suggest that T GFβ dysregulation during tumorigenesis may promote distinct breast cancerSubtypes.
Mammary Tumor–Derived Transplants as Breast Cancer Models to Evaluate Tumor–Immune Interactions and Therapeutic Responses
TLDR
The molecular diversity and immune complexity of mTDT should facilitate the dissection of mechanisms of breast cancer response to immunotherapy and improve the efficacy of immunotherapies.
Targeting Obesity-Induced Macrophages during Preneoplastic Growth Promotes Mammary Epithelial Stem/Progenitor Activity, DNA Damage, and Tumor Formation
TLDR
It is suggested that in obesity, macrophages reduce epithelial cells with DNA damage, which may limit the progression of preneoplastic breast lesions, and uncovers complex macrophage function within the evolving tumor microenvironment.
Radiation-Induced Reprogramming of Pre-Senescent Mammary Epithelial Cells Enriches Putative CD44+/CD24−/low Stem Cell Phenotype
TLDR
Results suggest that reprogramming of pre-senescent non-stem cells may play a significant role in both cancer and non-tumorigenic mammary epithelial populations following exposure to IR, a finding with important implications for both radiation therapy and radiation carcinogenesis.
Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype
TLDR
It is demonstrated that transduction of human breast luminal cells with hTERT/shp16 renders them immortal while remaining true to the luminal lineage including expression of functional ER (iHBECERpos), and proposed that iHBEC ERpos may serve to shed light on hitherto unappreciated differences in ER regulation and function between normal breast and breast cancer.
Densely ionizing radiation acts via the microenvironment to promote aggressive Trp53-null mammary carcinomas.
TLDR
The data suggest that carcinogenic effects of densely ionizing radiation are mediated by the microenvironment, which elicits more aggressive tumors compared with similar tumors arising in sham-irradiated hosts.
Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy
TLDR
These data show that radiation acts via nonmutational mechanisms to promote markedly immunosuppressive features of aggressive, radiation-preceded breast cancers, RP-BCs.
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