| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Pediatrics, General Hospital Salzburg (A.B., R.L., K.M., R.S., W.S., B.K.), and Department of Molecular Neurobiology and Cellular Physiology, Institute of Zoology, University of Salzburg (A.H.), A-5020 Salzburg, Austria
Address all correspondence and requests for reprints to: Dr. Barbara Kofler, Department of Pediatrics, General Hospital Salzburg, Muellner Hauptstrasse 48, A-5020 Salzburg, Austria. E-mail: b.kofler{at}lks.at.
Recently we have shown that galanin binding significantly correlates with survival in neuroblastoma patients, indicating a possible modulatory role of galanin receptors in neuroblastic tumor biology. However, the molecular mechanisms beyond this correlation have not been elucidated. Here, the cellular effects on activation of specific galanin receptor subtypes in human SH-SY5Y neuroblastoma cells were analyzed using a tetracycline-controlled expression system. Pharmacological studies confirmed the inducible expression of high affinity binding sites for galanin in SH-SY5Y cells transfected with the galanin receptors GalR1 (SY5Y/GalR1) and GalR2 (SY5Y/GalR2). Microphysiometry revealed that both receptor subtypes were able to mediate an intracellular signal upon galanin application. Interestingly, induction of receptor expression and treatment with 100 nM galanin resulted in a dramatic decrease in cell viability in SY5Y/GalR2 cells (93 ± 3%) compared with a less pronounced effect in SY5Y/GalR1 cells (19 ± 10%). The antiproliferative potency of galanin was 100-fold higher in SY5Y/GalR2 (50% effective concentration, 1.1 nM) than in SY5Y/GalR1 cells (50% effective concentration, 190 nM). Furthermore, activation of receptor expression and exposure to galanin resulted in apparent morphological changes indicative of apoptosis in SY5Y/GalR2 cells only. Induction of cell death by the apoptotic process was confirmed by poly-(ADP-ribose)-polymerase cleavage, caspase-3 activation, and the typical laddering of DNA. This study indicates that a high level of GalR2 expression is able to inhibit cell proliferation and induce apoptosis in neuroblastoma cells and therefore identifies GalR2 as a possible target for pharmacological intervention in neuroblastoma.
This article has been cited by other articles:
 |
|
 |
|
  T. Kanazawa, P. K. Kommareddi, T. Iwashita, B. Kumar, K. Misawa, Y. Misawa, I. Jang, T. S. Nair, Y. Iino, and T. E. Carey Galanin Receptor Subtype 2 Suppresses Cell Proliferation and Induces Apoptosis in p53 Mutant Head and Neck Cancer Cells Clin. Cancer Res., April 1, 2009; 15(7): 2222 - 2230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tofighi, B. Joseph, S. Xia, Z.-Q. D. Xu, B. Hamberger, T. Hokfelt, and S. Ceccatelli Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2) PNAS, February 19, 2008; 105(7): 2717 - 2722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Santic, S. M. Schmidhuber, R. Lang, I. Rauch, E. Voglas, N. Eberhard, J. W. Bauer, S. D. Brain, and B. Kofler Alarin is a vasoactive peptide PNAS, June 12, 2007; 104(24): 10217 - 10222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Agaram, P. Besmer, G. C. Wong, T. Guo, N. D. Socci, R. G. Maki, D. DeSantis, M. F. Brennan, S. Singer, R. P. DeMatteo, et al. Pathologic and Molecular Heterogeneity in Imatinib-Stable or Imatinib-Responsive Gastrointestinal Stromal Tumors Clin. Cancer Res., January 1, 2007; 13(1): 170 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Henson, R. R. Neubig, I. Jang, T. Ogawa, Z. Zhang, T. E. Carey, and N. J. D'Silva Galanin Receptor 1 Has Anti-proliferative Effects in Oral Squamous Cell Carcinoma J. Biol. Chem., June 17, 2005; 280(24): 22564 - 22571. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
