herg Encodes a K+ Current Highly Conserved in Tumors of Different Histogenesis: A Selective Advantage for Cancer Cells?

摘要: Abstract The human ether-a-go-go-related gene (herg) encodes a K+ current (IHERG) that plays fundamental role in heart excitability by regulating the action potential repolarization (IKr); mutations of this are responsible for chromosome 7-linked long QT syndrome (LQT2). In report, we show variety (n = 17) tumor cell lines different species (human and murine) distinct histogenesis (neuroblastoma, rhabdomyosarcoma, adenocarcinoma, lung microcytoma, pituitary tumors, insulinoma β-cells, monoblastic leukemia), novel inwardrectifier (IIR), which is biophysically pharmacologically similar to IHERG, can be recorded with patch-clamp technique. Northern blot experiments herg cDNA probe revealed both murine clones very high expression transcripts quantified at least three clearly identifiable bands, suggesting an alternative splicing HERG mRNA. Moreover, cloned encoding IIR from SH-SY5Y neuroblastoma. sequence result was practically identical already reported herg, indicating conservation tumors. Consistently, clone Xenopus oocytes showed encoded channel had substantially all biophysical pharmacological properties native described fdor cells. addition, studied, governs resting potential, whereas it could not detected either patch clamp or techniques cells obtained primary cultures parental tissues (sensory neurons myotubes), whose controlled classical anomalous rectifier current. This substitution profound impact on markedly depolarized tumors as compared normal These results suggest normally only expressed during early stages differentiation frozen neoplastic transformation, playing important pathophysiological regulatory mechanisms survival. fact, because its features, IIR, besides keeping within values required unlimited growth, also appear suitable afford selective advantage ischemic environment.