Document Detail

Constitutive activation of RANK disrupts mammary cell fate leading to tumorigenesis.
MedLine Citation:
PMID:  23766243     Owner:  NLM     Status:  MEDLINE    
Receptor Activator of NF-kappa B (RANK) pathway controls mammary gland development in mice but its role in mammary stem cell fate remains undefined. We show that constitutive RANK signaling expands luminal and basal mammary compartments including mammary stem and luminal progenitor cell pools and interferes with the generation of CD61+ and Sca1+ luminal cells and Elf5 expression. Impaired mammary cell commitment upon RANK overexpression leads to the accumulation of progenitors including K14+K8+ bipotent cells and the formation of heterogeneous tumors containing hyperplastic basal, luminal, and progenitor cells. RANK expression increases in wild-type mammary epithelia with age and parity, and spontaneous preneoplastic lesions express RANK and accumulate K14+K8+ cells. In human breast tumors, high RANK expression levels are also associated with altered mammary differentiation. These results suggest that increased RANK signaling interferes with mammary cell commitment, contributing to breast carcinogenesis.
Pasquale Pellegrini; Pellegrini Pasquale; Alex Cordero; Cordero Alex; Marta Ines Gallego; Gallego Marta Ines; William C Dougall; Dougall C William; Muñoz Purificación; Miguel Angel Pujana; Pujana Miguel Angel; Eva Gonzalez-Suarez; Gonzalez-Suarez Eva
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  31     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-10-07     Completed Date:  2014-05-07     Revised Date:  2014-11-03    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1954-65     Citation Subset:  IM    
Copyright Information:
© AlphaMed Press.
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MeSH Terms
Adenocarcinoma / genetics,  pathology
Aging / pathology
Breast Neoplasms / genetics,  pathology
Carcinogenesis / genetics,  pathology*
Cell Compartmentation
Cell Differentiation
Cell Lineage*
Cell Shape
Epithelium / pathology
Gene Expression Regulation, Neoplastic
Keratins / metabolism
Mammary Glands, Animal / metabolism,  pathology
Mammary Neoplasms, Experimental / genetics,  pathology
Mammary Tumor Virus, Mouse / physiology
Models, Biological
Precancerous Conditions / genetics,  pathology
Receptor Activator of Nuclear Factor-kappa B / genetics,  metabolism*
Stem Cells / metabolism
Reg. No./Substance:
0/Receptor Activator of Nuclear Factor-kappa B; 68238-35-7/Keratins
Erratum In:
Stem Cells. 2014 Feb;32(2):600
Note: Pasquale, Pellegrini [corrected to Pellegrini, Pasquale]; Alex, Cordero [corrected to Cordero, Alex]; Marta Ines, Gallego [corrected to Gallego, Marta Ines ]; William, Dougall C [corrected to Dougall, William C]; Miguel Angel, Pujana [corrected to Pujana, Miguel Angel]; Eva, Gonzalez-Suarez [corrected to Gonzalez-Suarez, Eva]

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