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

Davies, Gaynor, Martin, Tracey Amanda, Ye, Lin, Lewis-Russell, Jonathon M., Mason, Malcolm David and Jiang, Wen Guo 2008. Phospholipase-C gamma-1 (PLCγ-1) is critical in hepatocyte growth factor induced in vitro invasion and migration without affecting the growth of prostate cancer cells. Urologic Oncology: Seminars and Original Investigations 26 (4) , pp. 386-391. 10.1016/j.urolonc.2007.06.003

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Abstract

Background Phospholipase C gamma-1 (PLCγ-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 PLCγ-1. Methods A ribozyme transgene consisting of hammerhead ribozyme and antisense specific to PLCγ-1 was cloned into a PEF6 expression vector and transfected into PC-3 cells. RT-PCR and Western blotting confirmed knock down of PLCγ-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 PLCγ-1 manipulation. Results PC-3 cells stably transfected with PLCγ-1 ribozyme transgene (PC-3ΔPLCγ) manifested a reduction of PLCγ-1 expression at mRNA/protein levels. HGF/SF increased invasiveness (P < 0.01) and motility (P < 0.0001) of PC-3WT and PC-3PEF6 cells. In contrast, PLCγ-1 knock down PC-3ΔPLCγ cells had reduced invasiveness (P < 0.05) and motility (P < 0.01) compared with PC-3WT and PC-3PEF6 cells. Although there was a marginal change of cell growth in vitro, there was no difference in the rate of growth between PC-3ΔPLCγ, PC-3WT, and PC-3PEF6 cells. Conclusion Targeting PLCγ-1 by way of a hammerhead ribozyme to PLCγ-1 is an effective method in reducing invasive phenotype of prostate cancer. PLCγ-1 is a signalling intermediate that has prime influence on HGF induced cellular invasion and migration without affecting the growth of the cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: Ribozyme; HGF/SF; PLCγ-1; Prostate cancer; Migration; Invasion
Publisher: Elsevier
ISSN: 1078-1439
Last Modified: 07 Mar 2019 22:18
URI: http://orca-mwe.cf.ac.uk/id/eprint/25604

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