PMID- 19881541
OWN - NLM
STAT- MEDLINE
DCOM- 20100205
LR  - 20211020
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 29
IP  - 4
DP  - 2010 Jan 28
TI  - Wnt signaling activation and mammary gland hyperplasia in MMTV-LRP6 transgenic 
      mice: implication for breast cancer tumorigenesis.
PG  - 539-49
LID - 10.1038/onc.2009.339 [doi]
AB  - Although Wnt signaling activation is frequently observed in human breast cancer, 
      mutations in genes encoding intracellular components of the Wnt signaling pathway 
      are rare. We found that the expression of Wnt signaling co-receptor, LRP6, is 
      upregulated in a subset of human breast cancer tissues and cell lines. To examine 
      whether the overexpression of LRP6 in mammary epithelial cells is sufficient to 
      activate Wnt signaling and promote cell proliferation, we generated transgenic 
      mice overexpressing LRP6 in mammary epithelial cells driven by the mouse mammary 
      tumor virus (MMTV) promoter. We found that mammary glands from MMTV-LRP6 mice 
      exhibit significant Wnt activation evidenced by the translocation of beta-catenin 
      from membrane to cytoplasmic/nuclear fractions. The expression of several Wnt 
      target genes including Axin2, Cyclin D1 and c-Myc was also increased in MMTV-LRP6 
      mice. More importantly, mammary glands from virgin MMTV-LRP6 mice exhibit 
      significant hyperplasia, a precursor to breast cancer, when compared with 
      wild-type littermate controls. Several matrix metalloproteinases are upregulated 
      in MMTV-LRP6 mice that could contribute to the hyperplasia phenotype. Our results 
      suggest that Wnt signaling activation at the cell-surface receptor level can 
      contribute to breast cancer tumorigenesis.
FAU - Zhang, J
AU  - Zhang J
AD  - Department of Pediatrics, Washington University School of Medicine, St Louis, MO 
      63110, USA.
FAU - Li, Y
AU  - Li Y
FAU - Liu, Q
AU  - Liu Q
FAU - Lu, W
AU  - Lu W
FAU - Bu, G
AU  - Bu G
LA  - eng
GR  - R01CA100520/CA/NCI NIH HHS/United States
GR  - R01 CA100520-03/CA/NCI NIH HHS/United States
GR  - R01 CA100520-01A2/CA/NCI NIH HHS/United States
GR  - R01 CA124531/CA/NCI NIH HHS/United States
GR  - R01 CA100520-02/CA/NCI NIH HHS/United States
GR  - R01 CA100520-04/CA/NCI NIH HHS/United States
GR  - R01 CA100520/CA/NCI NIH HHS/United States
GR  - R01CA124531/CA/NCI NIH HHS/United States
GR  - R01 CA100520-05/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091102
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (LRP6 protein, human)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-6)
RN  - 0 (Lrp6 protein, mouse)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt3 Protein)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Cell Transformation, Neoplastic/genetics/*metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hyperplasia/genetics/metabolism
MH  - LDL-Receptor Related Proteins/genetics/*metabolism
MH  - Low Density Lipoprotein Receptor-Related Protein-6
MH  - Mammary Glands, Animal/*metabolism/*pathology
MH  - Mammary Neoplasms, Animal/drug therapy/genetics/*metabolism/pathology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *Signal Transduction
MH  - Wnt Proteins/genetics/*metabolism
MH  - Wnt3 Protein
PMC - PMC2813429
MID - NIHMS146777
EDAT- 2009/11/03 06:00
MHDA- 2010/02/06 06:00
PMCR- 2010/07/28
CRDT- 2009/11/03 06:00
PHST- 2009/11/03 06:00 [entrez]
PHST- 2009/11/03 06:00 [pubmed]
PHST- 2010/02/06 06:00 [medline]
PHST- 2010/07/28 00:00 [pmc-release]
AID - onc2009339 [pii]
AID - 10.1038/onc.2009.339 [doi]
PST - ppublish
SO  - Oncogene. 2010 Jan 28;29(4):539-49. doi: 10.1038/onc.2009.339. Epub 2009 Nov 2.