Document Detail


Common integration sites for MMTV in viral induced mouse mammary tumors.
MedLine Citation:
PMID:  18709449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) is used to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. It is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant inter-genomic distances. Genes commonly affected by MMTV insertion in multiple individual tumors include, the Wnt, FGF, RSpo gene families as well as eIF3e and Notch4. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long-lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all of the features ascribed to tissue-specific stem cells.
Authors:
Robert Callahan; Gilbert H Smith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review     Date:  2008-08-15
Journal Detail:
Title:  Journal of mammary gland biology and neoplasia     Volume:  13     ISSN:  1573-7039     ISO Abbreviation:  J Mammary Gland Biol Neoplasia     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-01     Completed Date:  2008-12-03     Revised Date:  2012-03-07    
Medline Journal Info:
Nlm Unique ID:  9601804     Medline TA:  J Mammary Gland Biol Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  309-21     Citation Subset:  IM    
Affiliation:
Mammary Gland Biology and Tumorigenesis Laboratory, National Cancer Institute, Building 37/Room 1118A, MSC4254, Bethesda, MD 20892, USA. rc54d@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA, Viral / metabolism
Epithelial Cells / metabolism
Female
Humans
Mammary Neoplasms, Animal / pathology*,  virology*
Mammary Tumor Virus, Mouse / genetics,  metabolism*
Mice
Models, Biological
Mutagenesis
Pregnancy
Signal Transduction
Grant Support
ID/Acronym/Agency:
Z99 CA999999/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Viral
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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