Changes in choline metabolism as potential biomarkers of phospholipase C{gamma}1 inhibition in human prostate cancer cells.
Mol Cancer Ther
; 8(5): 1305-11, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19417158
ABSTRACT
Phosphoinositide-specific phospholipase Cγ1 (PLCγ1) is activated downstream of many receptor tyrosine kinases to promote cell motility. Inhibition of this protein is being explored as a therapeutic strategy for blocking cancer cell invasion and metastasis. The clinical development of such cytostatic therapies requires the implementation of pharmacodynamic biomarkers of target modulation. In this study, we use magnetic resonance spectroscopy to explore metabolic biomarkers of PLCγ1 down-regulation in PC3LN3 prostate cancer cells. We show that inhibition of PLCγ1 via an inducible short hairpin RNA system causes a reduction in phosphocholine levels by up to 50% relative to the control as detected by (1)H and (31)P magnetic resonance spectroscopy analyses. This correlated with a rounded-up morphology and reduced cell migration. Interestingly, the fall in phosphocholine levels was not recorded in cells with constitutive PLCγ1 knockdown where the rounded-up phenotype was no longer apparent. This study reveals alterations in metabolism that accompany the cellular effects of PLCγ1 knockdown and highlights phosphocholine as a potential pharmacodynamic biomarker for monitoring the action of inhibitors targeting PLCγ1 signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosforilcolina
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Neoplasias da Próstata
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Fosfolipase C gama
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido