PMID- 11489839
OWN - NLM
STAT- MEDLINE
DCOM- 20011018
LR  - 20220310
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 7
IP  - 8
DP  - 2001 Aug
TI  - A hammerhead ribozyme suppresses expression of hepatocyte growth factor/scatter 
      factor receptor c-MET and reduces migration and invasiveness of breast cancer 
      cells.
PG  - 2555-62
AB  - PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF), via its receptor 
      c-MET, has been implicated to play a pivotal role in breast cancer development 
      and progression. This study examined a transgene-consisting of a combination of 
      U1snRNA, hammerhead ribozyme, and antisense, designed to inhibit c-met 
      expression-and its impact on the migration and in vitro invasion of breast cancer 
      cells. EXPERIMENTAL DESIGN: A hammerhead ribozyme targeting human c-MET was 
      cloned into a modified pZeoU1EcoSpe vector and transfected into breast cancer 
      cells MDA MB 231 and MCF-7 by electroporation. Expression of MET mRNA and protein 
      was determined. Migration and in vitro invasiveness of transfected cells were 
      also analyzed. RESULTS: Breast cancer cells were transfected with the 
      ribozyme-containing plasmids. Stable transfectants manifested an almost complete 
      loss of MET mRNA and protein, as shown by reverse transcription-PCR, Northern 
      blotting, and Western blotting, respectively, whereas the wild-type plasmid had 
      no effects. Met-ribozyme transfected cells exhibited reduced migration and in 
      vitro invasiveness through extracellular matrix (Matrigel), compared with the 
      wild-type cells and cells transfected with empty plasmid. CONCLUSIONS: These data 
      show that targeting c-MET by way of a hammerhead ribozyme encoding antisense to 
      c-MET is an effective approach in reducing the invasiveness of breast cancer 
      cells.
FAU - Jiang, W G
AU  - Jiang WG
AD  - University Department of Surgery, University of Wales College of Medicine, 
      Cardiff CF14 4XN, United Kingdom. jiangw@cf.ac.uk
FAU - Grimshaw, D
AU  - Grimshaw D
FAU - Lane, J
AU  - Lane J
FAU - Martin, T A
AU  - Martin TA
FAU - Abounader, R
AU  - Abounader R
FAU - Laterra, J
AU  - Laterra J
FAU - Mansel, R E
AU  - Mansel RE
LA  - eng
GR  - 1999:73/BCN_/Breast Cancer Now/United Kingdom
GR  - R01 NS32148/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (DNA, Antisense)
RN  - 0 (RNA, Catalytic)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Nuclear)
RN  - 0 (U1 small nuclear RNA)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
EIN - Clin Cancer Res 2002 Jan;8(1):300. Abounder R [corrected to Abounader R]
MH  - Base Sequence
MH  - Breast Neoplasms/genetics/*pathology/therapy
MH  - Cell Movement/genetics
MH  - DNA, Antisense/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Molecular Sequence Data
MH  - Neoplasm Invasiveness/genetics/prevention & control
MH  - Plasmids/genetics
MH  - Proto-Oncogene Proteins c-met/*genetics/metabolism
MH  - RNA, Catalytic/*genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Nuclear/genetics/metabolism
MH  - Time Factors
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2001/08/08 10:00
MHDA- 2001/10/19 10:01
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2001/10/19 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2001 Aug;7(8):2555-62.