| Chromatin effector Pygo2 regulates mammary tumor initiation and heterogeneity in MMTV-Wnt1 mice. | |
| | |
MedLine Citation:
|
PMID: 23334328 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Little is known about chromatin mechanisms that regulate tumor-initiating cells that are proposed to be responsible for tumor recurrence and relapse. We have previously shown that Pygopus 2 (Pygo2), a chromatin effector and context-dependent Wnt signaling coactivator, regulates mammary gland development by expanding epithelial stem/progenitor cells. However, the role of Pygo2 in mammary tumorigenesis in vivo remains to be addressed. In this study, we show that epithelia-specific ablation of Pygo2 in MMTV-Wnt1 transgenic mice results in delayed mammary ductal elongation, but the hyperbranching phenotype, aberrant accumulation of stem/progenitor-like cells, and canonical Wnt signaling output are largely unaffected. Chronic loss of Pygo2 significantly delays mammary tumor onset in MMTV-Wnt1 females, whereas acute deletion of Pygo2 in MMTV-Wnt1 tumor cells leads to a significant decrease in their tumor-initiating capability upon transplantation. Finally, we provide evidence supporting a role for Pygo2 in modulating the lineage potential of MMTV-Wnt1 tumor initiating cells. Collectively, our results suggest that Pygo2 acts at a step downstream of mammary stem cell accumulation to facilitate transformation, and that it regulates the tumor initiating capacity and lineage preference of the already transformed mammary cells, in MMTV-Wnt1 mice. These findings offer valuable insights into our understanding of the molecular basis of heterogeneity within breast tumors.Oncogene advance online publication, 21 January 2013; doi:10.1038/onc.2012.620. |
| | |
Authors:
|
K Watanabe; M Fallahi; X Dai |
Related Documents
:
|
17881898 - A transgenic mouse model for high content, cell cycle phenotype screening in live prima... 3206108 - Establishment of highly metastatic clones without tumorigenicity derived from dunn oste... 15380508 - Mouse models of human cancer as tools in drug development. 21160808 - Immunohistochemical and molecular genetic analyses of multiple sporadic gastrointestina... 19570088 - Tumor lysis syndrome after transcatheter arterial infusion of cisplatin and embolizatio... 6825078 - Effect of whole-body hyperthermia on cell survival, metastasis frequency, and host immu... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-21 |
Journal Detail:
|
Title: Oncogene Volume: - ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-21 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8711562 Medline TA: Oncogene Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion.
Next Document: Human skin neural crest progenitor cells are susceptible to BRAF(V600E)-induced transformation.