Abstract
We reported earlier on the oncogenic properties of
Grm1
by demonstrating that stable
Grm1
-mouse-melanocytic clones proliferate in the absence of growth supplement and anchorage
in vitro
. In addition these clones also exhibit aggressive tumorigenic phenotypes
in vivo
with short latency in tumor formation in both immunodeficient and syngeneic mice. We also detected strong activation of AKT in allograft tumors specifically AKT2 as the predominant isoform involved. In parallel we assessed several human melanoma biopsy samples and found again that AKT2 was the predominantly activated AKT in these human melanoma biopsies. In cultured stable
Grm1
-mouse melanocytic clones, as well as an mGlu1 expressing human melanoma cell line, C8161, stimulation of mGlu1 by its agonist led to the activation of AKT, while pre-incubation with mGlu1-antagonist abolished mGlu1-agonist-induced AKT activation. In addition, a reduction in tumor volume of
Grm1
-mouse-melanocytic-allografts was detected in the presence of small interfering AKT2 RNA (siAKT2). Taken together, these results showed that, in addition to the MAPK pathway previously reported being a downstream target of stimulated mGlu1, AKT2 is another downstream target in
Grm1
mediated melanocyte transformation.