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Institut für Pharmakologie und Toxikologie, Karl-von-Frisch-Str. 1, Philipps-Universität Marburg, 35043 Marburg, Germany

(Requests for offprints should be addressed to T Gudermann; Email: guderman{at}staff.uni-marburg.de)

Approximately 15–25% of all primary cancers of the lung are classified histologically as small cell lung carcinoma (SCLC), a subtype characterized by rapid growth and a poor prognosis. Neuropeptide hormones like bombesin/gastrin-releasing peptide, bradykinin or galanin are the principal mitogenic stimuli of this tumour entity. The mitogenic signal is transmitted into the cell via heptahelical neuropeptide hormone receptors, which couple to the heterotrimeric G proteins of the G_q/11 familiy. Subsequent activation of phospholipase Cß (PLCß) entails the activation of protein kinase C and the elevation of the intracellular calcium concentration. There is mounting evidence to support the notion that calcium mobilization is the key event that initiates different mitogen-activated protein kinase cascades. Neuropeptide-dependent proliferation of SCLC cells relies on parallel activation of the G_q/11/PLCß/Ras/extracellular signal-regulated kinase and the c-jun N-terminal kinase pathways, while selective engagement of either signalling cascade alone results in growth arrest and differentiation or apoptotic cell death. Basic experimental research has the potential to identify and validate novel therapeutic targets located at critical points of convergence of different mitogenic signal transduction pathways. In the case of SCLC, targeting the distinct components of the Ca²⁺ influx pathway as well as critical Ca²⁺-dependent cellular effectors may be rewarding in this regard.

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				M. Grzelinski, O. Pinkenburg, T. Buch, M. Gold, S. Stohr, H. Kalwa, T. Gudermann, and A. Aigner Critical Role of G{alpha}12 and G{alpha}13 for Human Small Cell Lung Cancer Cell Proliferation In vitro and Tumor Growth In vivo Clin. Cancer Res., March 1, 2010; 16(5): 1402 - 1415. [Abstract] [Full Text] [PDF]