PMID- 16510589
OWN - NLM
STAT- MEDLINE
DCOM- 20060418
LR  - 20081121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 5
DP  - 2006 Mar 1
TI  - Matrix metalloproteinases play an active role in Wnt1-induced mammary 
      tumorigenesis.
PG  - 2691-9
AB  - The Wnt signaling transduction pathway plays a critical role in the pathogenesis 
      of several murine and human epithelial cancers. Here, we have used mouse mammary 
      tumor virus (MMTV)-Wnt1 transgenic mice, which develop spontaneous mammary 
      adenocarcinoma, to examine whether matrix metalloproteinases (MMPs)--a family of 
      extracellular proteases implicated in multiple steps of cancer 
      progression--contributed to Wnt1-induced tumorigenesis. An analysis of the 
      expression of several MMPs by RT-PCR and in situ hybridization revealed an 
      increase in the expression of MMP-2, MMP-3, MMP-9, MMP-13, and MT1-MMP (MMP-14) 
      in hyperplastic glands and in mammary tumors of MMTV-Wnt1 transgenic mice. 
      Interestingly, whereas MMP-2, MMP-3, and MMP-9 were exclusively expressed by 
      stromal cells in mammary tumors, MMP-13 and MT1-MMP were expressed by transformed 
      epithelial cells in addition to the tumor stroma. To determine whether these MMPs 
      contributed to tumorigenesis, MMTV-Wnt1 mice were crossed with transgenic mice 
      overexpressing tissue inhibitor of metalloproteinase-2-a natural MMP inhibitor-in 
      the mammary gland. In the double MMTV-Wnt1/tissue inhibitor of 
      metalloproteinases-2 transgenic mice, we observed an increase in tumor latency 
      and a 26.3% reduction in tumor formation. Furthermore, these tumors grew at a 
      slower rate, exhibited an 18% decrease in proliferative rate, and a 12.2% 
      increase in apoptotic rate of the tumor cells in association with a deficit in 
      angiogenesis when compared with tumors from MMTV-Wnt1 mice. Thus, for the first 
      time, the data provides evidence for the active role of MMPs in Wnt1-induced 
      mammary tumorigenesis.
FAU - Blavier, Laurence
AU  - Blavier L
AD  - Division of Hematology/Oncology, Department of Pediatrics, USC Keck School of 
      Medicine, Los Angeles, California, USA.
FAU - Lazaryev, Alisa
AU  - Lazaryev A
FAU - Dorey, Frederick
AU  - Dorey F
FAU - Shackleford, Gregory M
AU  - Shackleford GM
FAU - DeClerck, Yves A
AU  - DeClerck YA
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Isoenzymes)
RN  - 0 (Wnt1 Protein)
RN  - 0 (Wnt1 protein, mouse)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Growth Processes/physiology
MH  - Female
MH  - Isoenzymes/biosynthesis
MH  - Mammary Glands, Animal/enzymology
MH  - Mammary Neoplasms, Experimental/blood supply/*enzymology/genetics/pathology
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Matrix Metalloproteinases/*biosynthesis
MH  - Mice
MH  - Mice, Transgenic
MH  - Neovascularization, Pathologic/metabolism/pathology
MH  - Promoter Regions, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis
MH  - Transgenes
MH  - Wnt1 Protein/*biosynthesis/genetics
EDAT- 2006/03/03 09:00
MHDA- 2006/04/19 09:00
CRDT- 2006/03/03 09:00
PHST- 2006/03/03 09:00 [pubmed]
PHST- 2006/04/19 09:00 [medline]
PHST- 2006/03/03 09:00 [entrez]
AID - 66/5/2691 [pii]
AID - 10.1158/0008-5472.CAN-05-2919 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Mar 1;66(5):2691-9. doi: 10.1158/0008-5472.CAN-05-2919.