Molecular and functional characterization of non voltage-operated Ca2+ entry in gastrointestinal neuroendocrine tumor cells

摘要

Ca²⁺ entry through non-voltage operated channels serves as a key signaling component for tumor progression in a variety of cancers including prostate, colon and breast. As a starting point for an inquiry into the role of Ca²⁺ signaling pathways in gastroenteropancreatic neuroendocrine cancers, including carcinoid, we characterized Ca²⁺ entry in a set of human carcinoid cell lines originating in the foregut, midgut and hindgut. In the current study, we provide molecular and functional evidence for store-operated and other non-voltage operated Ca²⁺ permeable channels in carcinoid tumor cell lines. RT-PCR technique was used to profile an array of non voltage-operated Ca²⁺ channels in carcinoid cell lines. Live-cell imaging methods were used to functionally assess store operated Ca²⁺ entry (SOCE) following depletion of ER Ca²⁺ stores by cyclopiazonic acid. Treatment with pharmacological inhibitors of SOCE generally reduced Ca²⁺ entry. We also demonstrated that SOCE in some carcinoid cell lines was activated by neurotransmitter suggesting that Ca²⁺ entry through specific channels may be important for mediating neural, paracrine or autocrine signals in the gut in health and disease such as carcinoid cancer.