Highly Ca2+ permeable receptor potential channel vanilloid type 6 (TRPV6)
modulates a variety of biological functions including calcium-dependent cell
growth and apoptosis. So far, the role of TRPV6 in controlling growth of
pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study,
we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET
cells. Furthermore, we evaluate the impact of TRPV6 on intracellular calcium,
the activity of nuclear factor of activated T-cells (NFAT) and proliferation
of BON-1 cells. TRPV6 expression was assessed by real-time PCR and Western
blot. TRPV6 mRNA expression and protein production were down-regulated by
siRNA. Changes in intracellular calcium levels were detected by fluorescence
calcium imaging (fura-2/AM). NFAT activity was studied by NFAT reporter assay;
cell proliferation by bromodeoxyuridine (BrdU), MTT and propidium iodine
staining. TRPV6 mRNA and protein are present in BON-1 and QGP-1 NET-cells.
Down-regulation of TRPV6 attenuates BON-1 cell proliferation. TRPV6 down-
regulation is associated with decreased Ca2+ response pattern and reduced NFAT
activity. In conclusion, TRPV6 is expressed in pancreatic NETs and modulates
cell proliferation via Ca2+-dependent mechanism, which is accompanied by NFAT
activation
