PMID- 18709449
OWN - NLM
STAT- MEDLINE
DCOM- 20081203
LR  - 20211020
IS  - 1573-7039 (Electronic)
IS  - 1083-3021 (Print)
IS  - 1083-3021 (Linking)
VI  - 13
IP  - 3
DP  - 2008 Sep
TI  - Common integration sites for MMTV in viral induced mouse mammary tumors.
PG  - 309-21
LID - 10.1007/s10911-008-9092-6 [doi]
AB  - 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.
FAU - Callahan, Robert
AU  - Callahan R
AD  - Mammary Gland Biology and Tumorigenesis Laboratory, National Cancer Institute, 
      Building 37/Room 1118A, MSC4254, Bethesda, MD 20892, USA. rc54d@nih.gov
FAU - Smith, Gilbert H
AU  - Smith GH
LA  - eng
GR  - Z99 CA999999/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Review
DEP - 20080815
PL  - United States
TA  - J Mammary Gland Biol Neoplasia
JT  - Journal of mammary gland biology and neoplasia
JID - 9601804
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Animals
MH  - DNA, Viral/metabolism
MH  - Epithelial Cells/metabolism
MH  - Female
MH  - Humans
MH  - Mammary Neoplasms, Animal/*pathology/*virology
MH  - Mammary Tumor Virus, Mouse/genetics/*metabolism
MH  - Mice
MH  - Models, Biological
MH  - Mutagenesis
MH  - Pregnancy
MH  - Signal Transduction
PMC - PMC3104473
MID - NIHMS293545
EDAT- 2008/08/19 09:00
MHDA- 2008/12/17 09:00
PMCR- 2011/05/31
CRDT- 2008/08/19 09:00
PHST- 2008/06/26 00:00 [received]
PHST- 2008/07/04 00:00 [accepted]
PHST- 2008/08/19 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/19 09:00 [entrez]
PHST- 2011/05/31 00:00 [pmc-release]
AID - 10.1007/s10911-008-9092-6 [doi]
PST - ppublish
SO  - J Mammary Gland Biol Neoplasia. 2008 Sep;13(3):309-21. doi: 
      10.1007/s10911-008-9092-6. Epub 2008 Aug 15.