The expression and potential
biological functions of
G protein-coupled receptor kinase 6 (GRK6) in human
glioma are tested in this study. We show that
protein and
mRNA expression of GRK6 in human
glioma tissues was significantly higher than that in the normal brain tissues. Further immunohistochemistry assay analyzing total 118 human
glioma tissues showed that GRK6 over-expression was correlated with
glioma pathologic grade and patients' Karnofsky performance status (KPS) score. At the molecular level, in the GRK6-low H4
glioma cells, forced over-expression of GRK6 promoted cell proliferation. Reversely,
siRNA-mediated knockdown of GRK6 in the U251MG (GRK6-high) cells led to proliferation inhibition and cell cycle arrest. Intriguingly, GRK6 could also be an important
temozolomide resistance factor.
Temozolomide-induced cytotoxicity was prominent only in GRK6-low H4
glioma cells. On the other hand, knockdown of GRK6 by targeted
siRNA sensitized U251MG cells (GRK6-high) to
temozolomide. Thus, GRK6 over-expression in
glioma is important for cell proliferation and
temozolomide resistance.