PMID- 15264243
OWN - NLM
STAT- MEDLINE
DCOM- 20040831
LR  - 20220310
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 60
IP  - 4
DP  - 2004 Sep 1
TI  - Targeting the HGF/SF receptor c-met using a hammerhead ribozyme transgene reduces 
      in vitro invasion and migration in prostate cancer cells.
PG  - 317-24
AB  - BACKGROUND: Hepatocyte growth factor scatter factor (HGF/SF) elicits a number of 
      biological activities including invasion and migration through activation of its 
      tyrosine kinase receptor c-Met. Over expression of c-Met has been implicated in 
      prostate cancer development and progression. This study examined the effect of a 
      ribozyme transgene, designed to inhibit human c-Met expression, and its impact on 
      in vitro invasion and migration in prostate cancer. METHODS: A transgene (Met 
      560) consisting of U1 snRNA, hammerhead ribozyme, and antisense was cloned into a 
      modified pZeoU1-EcoSpe vector and transfected into DU-145 cells. The effect of 
      HGF/SF was tested on prostate cancer cells whose expression of c-Met had been 
      blocked by way of a ribozyme transgene. RESULTS: Met 560 stable transfectants 
      (DU-145(+/+)) manifested a complete loss of c-Met expression at mRNA and protein 
      levels. In contrast, control plasmid (DU-145(+/-)) and wild-type DU-145 cells 
      (DU-145(-/-)) had similar levels of c-Met expression. HGF/SF significantly 
      increased the in vitro invasiveness (mean 47.71 +/- SE 7.75; P < 0.01 vs. control 
      24.14 +/- 1.34), and migration (mean 48.44 +/- SE 3.51; P < 0.01 vs. control 
      22.95 +/- 1.47) of DU-145(-/-) cells, respectively. Similarly, HGF/SF also 
      increased the invasion (62.33 +/- 6.34; P < 0.001 vs. control 24.5 +/- 2.35) and 
      migration (46.14 +/- 2.26; P < 0.01 vs. control 21.82 +/- 1.62) of DU-145(+/-) 
      cells. In contrast, DU-145(+/+) cells had lost its response to HGF/SF induced 
      invasion (22.33 +/- 2.08; P > 0.05 vs. control 23.5 +/- 2.11) and migration 
      (24.12 +/- 0.86; P > 0.05 vs. control 23.27 +/- 0.81). CONCLUSIONS: Targeting the 
      HGF/SF receptor by way of a hammerhead ribozyme encoding antisense to c-Met, is 
      an effective method to reduce the invasive or migration potential in prostate 
      cancer, and may have important therapeutic implications.
FAU - Davies, Gaynor
AU  - Davies G
AD  - Metastasis Research Group, University Department of Surgery, University of Wales 
      College of Medicine, Heath Park, Cardiff, United Kingdom. DAVIESG11@cf.ac.uk
FAU - Watkins, Gareth
AU  - Watkins G
FAU - Mason, Malcolm D
AU  - Mason MD
FAU - Jiang, Wen G
AU  - Jiang WG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (RNA, Catalytic)
RN  - 0 (RNA, Messenger)
RN  - 0 (hammerhead ribozyme)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - *Cell Movement
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Genetic Therapy/*methods
MH  - Humans
MH  - Male
MH  - *Neoplasm Invasiveness
MH  - Prostatic Neoplasms/genetics/*pathology
MH  - Proto-Oncogene Proteins c-met/*biosynthesis/*pharmacology
MH  - RNA, Catalytic/*genetics
MH  - RNA, Messenger/analysis
MH  - Transfection
MH  - *Transgenes
MH  - Tumor Cells, Cultured
EDAT- 2004/07/21 05:00
MHDA- 2004/09/01 05:00
CRDT- 2004/07/21 05:00
PHST- 2004/07/21 05:00 [pubmed]
PHST- 2004/09/01 05:00 [medline]
PHST- 2004/07/21 05:00 [entrez]
AID - 10.1002/pros.20068 [doi]
PST - ppublish
SO  - Prostate. 2004 Sep 1;60(4):317-24. doi: 10.1002/pros.20068.