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SHR Neuro Krebs Kardio Lipid

Sigl, V; Owusu-Boaitey, K; Joshi, PA; Kavirayani, A; Wirnsberger, G; Novatchkova, M; Kozieradzki, I; Schramek, D; Edokobi, N; Hersl, J; Sampson, A; Odai-Afotey, A; Lazaro, C; Gonzalez-Suarez, E; Pujana, MA; Cimba, F; Heyn, H; Vidal, E; Cruickshank, J; Berman, H; Sarao, R; Ticevic, M; Uribesalgo, I; Tortola, L; Rao, S; Tan, Y; Pfeiler, G; Lee, EY; Bago-Horvath, Z; Kenner, L; Popper, H; Singer, C; Khokha, R; Jones, LP; Penninger, JM.
RANKL/RANK control Brca1 mutation- .
Cell Res. 2016; 26(7):761-774 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kenner Lukas
Popper Helmuth
Wirnsberger Gerhard
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Number of Figures: 4
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Abstract:
Breast cancer is the most common female cancer, affecting approximately one in eight women during their life-time. Besides environmental triggers and hormones, inherited mutations in the breast cancer 1 (BRCA1) or BRCA2 genes markedly increase the risk for the development of breast cancer. Here, using two different mouse models, we show that genetic inactivation of the key osteoclast differentiation factor RANK in the mammary epithelium markedly delayed onset, reduced incidence, and attenuated progression of Brca1;p53 mutation-driven mammary cancer. Long-term pharmacological inhibition of the RANK ligand RANKL in mice abolished the occurrence of Brca1 mutation-driven pre-neoplastic lesions. Mechanistically, genetic inactivation of Rank or RANKL/RANK blockade impaired proliferation and expansion of both murine Brca1;p53 mutant mammary stem cells and mammary progenitors from human BRCA1 mutation carriers. In addition, genome variations within the RANK locus were significantly associated with risk of developing breast cancer in women with BRCA1 mutations. Thus, RANKL/RANK control progenitor cell expansion and tumorigenesis in inherited breast cancer. These results present a viable strategy for the possible prevention of breast cancer in BRCA1 mutant patients.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
BRCA1 Protein - genetics
BRCA2 Protein - genetics
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Proliferation - drug effects
Cells, Cultured -
DNA Damage - drug effects
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Estrogen Receptor alpha - metabolism
Female -
Genotype -
Humans -
Mice -
Mice, Inbred C57BL -
Mice, Transgenic -
RANK Ligand - antagonists & inhibitors
RANK Ligand - genetics
RANK Ligand - metabolism
Receptor Activator of Nuclear Factor-kappa B - genetics
Receptor Activator of Nuclear Factor-kappa B - metabolism
Receptors, Progesterone - metabolism
Recombinant Fusion Proteins - pharmacology
Recombinant Fusion Proteins - therapeutic use
Stem Cells - cytology
Stem Cells - metabolism
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism

Find related publications in this database (Keywords)
BRCA1
RANK
RANKL
inherited breast cancer
mammary progenitor cells
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