JOURNAL ARTICLE

Phospholipase-C gamma-1 (PLCgamma-1) is critical in hepatocyte growth factor induced in vitro invasion and migration without affecting the growth of prostate cancer cells

Gaynor Davies, Tracey A Martin, Lin Ye, Jonathon M Lewis-Russell, Malcolm D Mason, Wen G Jiang
Urologic Oncology 2008, 26 (4): 386-91
18367108

BACKGROUND: Phospholipase C gamma-1 (PLCgamma-1) is an intracellular signalling molecule regulating a number of biological processes including transporter mechanisms, transcription factors, and scaffolding proteins mediating cytoskeleton and membrane trafficking. Hepatocyte growth factor (HGF) is a pleiotrophic factor and a mediator of metastatic spread. This study sought to determine the effect of HGF on the invasive and migratory potential of prostate cancer cells targeted by a ribozyme transgene to PLCgamma-1.

METHODS: A ribozyme transgene consisting of hammerhead ribozyme and antisense specific to PLCgamma-1 was cloned into a PEF6 expression vector and transfected into PC-3 cells. RT-PCR and Western blotting confirmed knock down of PLCgamma-1. In vitro invasion and a cytodex-2 bead motility assays with in vitro and in vivo growth models were used to assess the impact of PLCgamma-1 manipulation.

RESULTS: PC-3 cells stably transfected with PLCgamma-1 ribozyme transgene (PC-3(DeltaPLC)gamma) manifested a reduction of PLCgamma-1 expression at mRNA/protein levels. HGF/SF increased invasiveness (P < 0.01) and motility (P < 0.0001) of PC-3(WT) and PC-3(PEF6) cells. In contrast, PLCgamma-1 knock down PC-3(DeltaPLC)gamma cells had reduced invasiveness (P < 0.05) and motility (P < 0.01) compared with PC-3(WT) and PC-3(PEF6) cells. Although there was a marginal change of cell growth in vitro, there was no difference in the rate of growth between PC-3(DeltaPLC)gamma, PC-3(WT), and PC-3(PEF6) cells.

CONCLUSION: Targeting PLCgamma-1 by way of a hammerhead ribozyme to PLCgamma-1 is an effective method in reducing invasive phenotype of prostate cancer. PLCgamma-1 is a signalling intermediate that has prime influence on HGF induced cellular invasion and migration without affecting the growth of the cells.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
18367108
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"