PMID- 15897450
OWN - NLM
STAT- MEDLINE
DCOM- 20050804
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 102
IP  - 21
DP  - 2005 May 24
TI  - Overexpression of LMO4 induces mammary hyperplasia, promotes cell invasion, and 
      is a predictor of poor outcome in breast cancer.
PG  - 7659-64
AB  - The zinc finger protein LMO4 is overexpressed in a high proportion of breast 
      carcinomas. Here, we report that overexpression of a mouse mammary tumor virus 
      (MMTV)-Lmo4 transgene in the mouse mammary gland elicits hyperplasia and mammary 
      intraepithelial neoplasia or adenosquamous carcinoma in two transgenic strains 
      with a tumor latency of 13-18 months. To investigate cellular processes 
      controlled by LMO4 and those that may be deregulated during oncogenesis, we used 
      RNA interference. Down-regulation of LMO4 expression reduced proliferation of 
      human breast cancer cells and increased differentiation of mouse mammary 
      epithelial cells. Furthermore, small-interfering-RNA-transfected breast cancer 
      cells (MDA-MB-231) had a reduced capacity to migrate and invade an extracellular 
      matrix. Conversely, overexpression of LMO4 in noninvasive, immortalized human 
      MCF10A cells promoted cell motility and invasion. Significantly, in a cohort of 
      159 primary breast cancers, high nuclear levels of LMO4 were an independent 
      predictor of death from breast cancer. Together, these findings suggest that 
      deregulation of LMO4 in breast epithelium contributes directly to breast 
      neoplasia by altering the rate of cellular proliferation and promoting cell 
      invasion.
FAU - Sum, Eleanor Y M
AU  - Sum EY
AD  - The Walter and Eliza Hall Institute of Medical Research and Bone Marrow Research 
      Laboratories, 1G Royal Parade, Parkville VIC 3050, Australia.
FAU - Segara, Davendra
AU  - Segara D
FAU - Duscio, Belinda
AU  - Duscio B
FAU - Bath, Mary L
AU  - Bath ML
FAU - Field, Andrew S
AU  - Field AS
FAU - Sutherland, Robert L
AU  - Sutherland RL
FAU - Lindeman, Geoffrey J
AU  - Lindeman GJ
FAU - Visvader, Jane E
AU  - Visvader JE
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050516
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA Primers)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (LIM Domain Proteins)
RN  - 0 (Lmo4 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Blotting, Western
MH  - Breast Neoplasms/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - DNA Primers
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - *Gene Expression
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Hyperplasia/metabolism
MH  - Immunohistochemistry
MH  - LIM Domain Proteins
MH  - Mammary Glands, Animal/metabolism/*pathology
MH  - Mammary Tumor Virus, Mouse
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Neoplasm Invasiveness/*genetics
MH  - New South Wales
MH  - RNA Interference
MH  - Risk Factors
MH  - Transcription Factors/genetics/*metabolism
MH  - Transfection
MH  - Transgenes/genetics
PMC - PMC1140463
EDAT- 2005/05/18 09:00
MHDA- 2005/08/05 09:00
PMCR- 2005/11/24
CRDT- 2005/05/18 09:00
PHST- 2005/05/18 09:00 [pubmed]
PHST- 2005/08/05 09:00 [medline]
PHST- 2005/05/18 09:00 [entrez]
PHST- 2005/11/24 00:00 [pmc-release]
AID - 0502990102 [pii]
AID - 01027659 [pii]
AID - 10.1073/pnas.0502990102 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2005 May 24;102(21):7659-64. doi: 
      10.1073/pnas.0502990102. Epub 2005 May 16.