Involvement of the γ1 subunit of the large-conductance Ca2+-activated K+ channel in the proliferation of human somatostatinoma cells.

Pancreatic neuroendocrine tumors (pNETs) occur due to the abnormal growth of pancreatic islet cells and predominantly develop in the duodenal-pancreatic region. Somatostatinoma is one of the pNETs associated with tumors of pancreatic δ cells, which produce and secrete somatostatin. Limited information is currently available on the pathogenic mechanisms of somatostatinoma. The large-conductance Ca2+-activated K+ (BK Ca) channel is expressed in several types of cancer cells and regulates cell proliferation, migration, invasion, and metastasis. In the present study, the functional expression of the BK Ca channel was examined in a human somatostatinoma QGP-1 cell line. In QGP-1 cells, outward currents were elicited by membrane depolarization at pCa 6.5 (300 nM) in the pipette solution and inhibited by the specific BK Ca channel blocker, paxilline. Paxilline-sensitive currents were detected, even at pCa 8.0 (10 nM) in the pipette solution, in QGP-1 cells. In addition to the α and β2-4 subunits of the BK Ca channel, the novel regulatory γ1 subunit (BK Ca γ1) was co-localized with the α subunit in QGP-1 cells. Paxilline-sensitive currents at pCa 8.0 in the pipette solution were reduced by the siRNA knockdown of BK Ca γ1. Store-operated Ca2+ entry was smaller in BK Ca γ1 siRNA-treated QGP-1 cells. The proliferation of QGP-1 cells was attenuated by paxilline or the siRNA knockdown of BK Ca γ1. These results strongly suggest that BK Ca γ1 facilitates the proliferation of human somatostatinoma cells. Therefore, BK Ca γ1 may be a novel therapeutic target for somatostatinoma. • Somatostatinoma is a pancreatic neuroendocrine tumor with high malignancy. • Somatostatinoma QGP-1 cells have large-conductance Ca2+-activated K+ (BK Ca) currents. • The γ1 subunit of BK Ca channel (BK Ca γ1) was functionally expressed in QGP-1 cells. • The proliferation of QGP-1 cells was facilitated by the presence of BK Ca γ1. • BK Ca γ1 may be a novel therapeutic target for somatostatinoma. [ABSTRACT FROM AUTHOR]