B-Raf deficiency impairs tumor initiation and progression in a murine breast cancer model.
Animals
Breast Neoplasms
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Cell Transformation, Neoplastic
/ genetics
Disease Models, Animal
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
MAP Kinase Signaling System
Mammary Neoplasms, Animal
/ genetics
Mice
Mice, Knockout
Mutation
Proto-Oncogene Proteins A-raf
/ genetics
Proto-Oncogene Proteins B-raf
/ deficiency
Proto-Oncogene Proteins c-raf
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
15
11
2017
accepted:
11
12
2018
revised:
22
11
2018
pubmed:
20
1
2019
medline:
5
3
2019
entrez:
20
1
2019
Statut:
ppublish
Résumé
Copy number gains, point mutations and epigenetic silencing events are increasingly observed in genes encoding elements of the Ras/Raf/MEK/ERK signaling axis in human breast cancer. The three Raf kinases A-Raf, B-Raf, and Raf-1 have an important role as gatekeepers in ERK pathway activation and are often dysregulated by somatic alterations of their genes or by the aberrant activity of receptor tyrosine kinases (RTKs) and Ras-GTPases. B-Raf represents the most potent Raf isoform and a critical effector downstream of RTKs and RAS proteins. Aberrant RTK signaling is mimicked by the polyoma middle T antigen (PyMT), which activates various oncogenic signaling pathways, incl. the RAS/ERK axis, in a similar manner as RTKs in human breast cancer. Mammary epithelial cell directed expression of PyMT in mice by the MMTV-PyMT transgene induces mammary hyperplasia progressing over adenoma to metastatic breast cancer with an almost complete penetrance. To understand the functional role of B-Raf in this model for luminal type B breast cancer, we crossed MMTV-PyMT mice with animals that either lack B-Raf expression in the mammary gland or express the signaling impaired B-Raf
Identifiants
pubmed: 30659267
doi: 10.1038/s41388-018-0663-8
pii: 10.1038/s41388-018-0663-8
doi:
Substances chimiques
Braf protein, mouse
EC 2.7.11.1
Proto-Oncogene Proteins A-raf
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Proto-Oncogene Proteins c-raf
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1324-1339Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 850 B4
Pays : International
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 850 B7
Pays : International
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 850 B7
Pays : International
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