PMID- 16618731
OWN - NLM
STAT- MEDLINE
DCOM- 20060607
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 8
DP  - 2006 Apr 15
TI  - Id1 transcription inhibitor-matrix metalloproteinase 9 axis enhances invasiveness 
      of the breakpoint cluster region/abelson tyrosine kinase-transformed leukemia 
      cells.
PG  - 4108-16
AB  - Breakpoint cluster region/Abelson (BCR/ABL) tyrosine kinase enhances the ability 
      of leukemia cells to infiltrate various organs. We show here that expression of 
      the helix-loop-helix transcription factor Id1 is enhanced by BCR/ABL in a signal 
      transducer and activator of transcription 5 (STAT5)-dependent manner. Enhanced 
      expression of Id1 plays a key role in BCR/ABL-mediated cell invasion. 
      Down-regulation of Id1 in BCR/ABL leukemia cells by the antisense cDNA 
      significantly reduced their invasive capability through the Matrigel membrane and 
      their ability to infiltrate hematopoietic and nonhematopoietic organs resulting 
      in delayed leukemogenesis in mice. The Id1-promoted cell invasiveness was 
      seemingly mediated by matrix metalloproteinase 9 (MMP9). Transactivation of MMP9 
      promoter in BCR/ABL cells was dependent on Id1 and abrogation of the MMP9 
      catalytic activity by a metalloproteinase inhibitor or blocking antibody 
      decreased invasive capacity of leukemia cells. These data suggest that 
      BCR/ABL-STAT5-Id1-MMP9 pathway may play a critical role in BCR/ABL-mediated 
      leukemogenesis by enhancing invasiveness of leukemia cells.
FAU - Nieborowska-Skorska, Margaret
AU  - Nieborowska-Skorska M
AD  - Department of Microbiology and Immunology, School of Medicine, Temple University, 
      Philadelphia, Pennsylvania 19140, USA.
FAU - Hoser, Grazyna
AU  - Hoser G
FAU - Rink, Lori
AU  - Rink L
FAU - Malecki, Maciej
AU  - Malecki M
FAU - Kossev, Plamen
AU  - Kossev P
FAU - Wasik, Mariusz A
AU  - Wasik MA
FAU - Skorski, Tomasz
AU  - Skorski T
LA  - eng
GR  - CA89194/CA/NCI NIH HHS/United States
GR  - R01 CA89052/CA/NCI NIH HHS/United States
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 (Idb1 protein, mouse)
RN  - 0 (Inhibitor of Differentiation Protein 1)
RN  - 0 (STAT5 Transcription Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Cell Transformation, Neoplastic/*metabolism
MH  - Fusion Proteins, bcr-abl
MH  - Hematopoietic Stem Cells/metabolism/physiology
MH  - Inhibitor of Differentiation Protein 1/biosynthesis/genetics/*metabolism
MH  - Leukemia, Experimental/*enzymology/genetics/pathology
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Invasiveness
MH  - Promoter Regions, Genetic
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - STAT5 Transcription Factor/metabolism
MH  - Transcriptional Activation
EDAT- 2006/04/19 09:00
MHDA- 2006/06/08 09:00
CRDT- 2006/04/19 09:00
PHST- 2006/04/19 09:00 [pubmed]
PHST- 2006/06/08 09:00 [medline]
PHST- 2006/04/19 09:00 [entrez]
AID - 66/8/4108 [pii]
AID - 10.1158/0008-5472.CAN-05-1584 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Apr 15;66(8):4108-16. doi: 10.1158/0008-5472.CAN-05-1584.