Arunachalam Sasi, Zhelay Tetyana, Giovannucci David R
Department of Neurosciences, University of Toledo College of Medicine Toledo OH 43614, USA.
Int J Physiol Pathophysiol Pharmacol. 2010 May 19;2(2):125-136.
Ca(2+) 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 Ca(2+) signaling pathways in gastroenteropancreatic neuroendocrine cancers, including carcinoid, we characterized Ca(2+) 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 Ca(2+) permeable channels in carcinoid tumor cell lines. RT-PCR technique was used to profile an array of non voltage-operated Ca(2+) channels in carcinoid cell lines. Live-cell imaging methods were used to functionally assess store operated Ca(2+) entry (SOCE) following depletion of ER Ca(2+) stores by cyclopiazonic acid. Treatment with pharmacological inhibitors of SOCE generally reduced Ca(2+) entry. We also demonstrated that SOCE in some carcinoid cell lines was activated by neurotransmitter suggesting that Ca(2+) 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.
通过非电压门控通道的钙离子内流是包括前列腺癌、结肠癌和乳腺癌在内的多种癌症肿瘤进展的关键信号成分。作为探究钙离子信号通路在胃肠胰神经内分泌癌（包括类癌）中作用的起点，我们对一组源自前肠、中肠和后肠的人类类癌细胞系中的钙离子内流进行了表征。在本研究中，我们提供了类癌肿瘤细胞系中储存式操作及其他非电压门控钙离子通透通道的分子和功能证据。采用逆转录聚合酶链反应（RT-PCR）技术分析类癌细胞系中一系列非电压门控钙离子通道。利用活细胞成像方法，在经环匹阿尼酸耗尽内质网钙离子储存后，从功能上评估储存式操作钙离子内流（SOCE）。用SOCE的药理学抑制剂处理通常会减少钙离子内流。我们还证明，某些类癌细胞系中的SOCE可被神经递质激活，这表明通过特定通道的钙离子内流对于在健康和疾病（如类癌）状态下介导肠道中的神经、旁分泌或自分泌信号可能很重要。
