Abstract
BackgroundIn prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray.Methodology/Principal FindingsPhosphorylated Akt immunoreactivity (pAkt-IR) scores were available in the database. CB1 receptor immunoreactivity (CB1IR) was rescored from previously published data using the same scale as pAkt-IR. There was a highly significant correlation between CB1IR and pAkt-IR. Further, cases with high expression levels of both biomarkers were much more likely to have a more severe form of the disease at diagnosis than those with low expression levels. The two biomarkers had additive effects, rather than an interaction, upon disease-specific survival.Conclusions/SignificanceThe present study provides data that is consistent with the hypothesis that at a high CB1 receptor expression, the Akt signalling pathway becomes operative.
Highlights
The endocannabinoid system, comprising the G-protein coupled CB1 and CB2 receptors, their endogenous ligands anandamide and 2-arachidonoylglycerol, and their synthetic and catabolic enzymes, has been shown to be involved in the control of proliferation, migration and invasive behaviour of a wide variety of cancer cells [1,2,3,4,5]
This correlation, significant, could be induced between two independent variables by a third factor: if parameter A, for example, induced both phosphorylated Akt (pAkt) and at the same time increased the synthesis of CB1 receptors, a correlation between Phosphorylated Akt immunoreactivity (pAkt-IR) and nCB1IR would be seen
In the tissue microarray, the pEGFR-IR and ErbB2-IR scores were correlated with pAkt-IR in the tumour tissue (Table 1 and [32])
Summary
The endocannabinoid (eCB) system, comprising the G-protein coupled CB1 and CB2 receptors, their endogenous ligands anandamide and 2-arachidonoylglycerol, and their synthetic and catabolic enzymes, has been shown to be involved in the control of proliferation, migration and invasive behaviour of a wide variety of cancer cells [1,2,3,4,5]. The human prostate expresses functionally active CB1 receptors [6], and anandamide reduces the rate of epidermal growth factor- (EGF) and prolactin-stimulated growth of human prostate cancer cell lines in a manner involving activation of CB1 receptors [7,8]. Inhibition of the synthesis of 2arachidonoylglycerol or transfection of cells with fatty acid amide hydrolase (FAAH), the enzyme responsible for the hydrolysis of anandamide, increases the invasivity of PC-3 cells in vitro [18,20] These data are all consistent with the notion that the eCB system, in addition to having a wealth of other regulatory properties in the body [21], plays a role in the local control of cancer cell spread. We have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray
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