The cannabinoid receptor inverse agonist AM251 regulates the expression of the EGF receptor and its ligands via destabilization of oestrogen-related receptor α protein.

ABSTRACT:

Background and purpose

AM251 is an inverse agonist of the cannabinoid 1 receptor (CB(1)R) that can exert 'off-target' effects in vitro and in CB(1)R knock-out mice. AM251 is also potent at modulating tumour cell growth, suggesting that growth factor-mediated oncogenic signalling could be regulated by AM251. Since dysregulation of the EGF receptor has been associated with carcinogenesis, we examined AM251 regulation of EGF receptor (EGFR) expression and function.

Experimental approach

The various biological functions of AM251 were measured in CB(1)R-negative human cancer cells. Pharmacological and genetic approaches were used to validate the data.

Key results

The mRNA levels for EGFR and its associated ligands, including HB-EGF, were induced several fold in PANC-1 and

SUBMITTER: Fiori JL 

PROVIDER: S-EPMC3195923 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature