HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Rapamycin inhibits proliferation of human neuroblastoma cells without suppression of MycN.

Abstract
MYCN and insulin-like growth factor (IGF) system are important for the pathogenesis and development of neuroblastoma. We previously reported evidence of a direct linkage between MycN and the IGF system in KP-N-RT human neuroblastoma cells, where IGF-I induced both MycN expression at the RNA level and G1-S cell cycle progression through the IGF-I receptor (IGF-IR)/ MEK/ mitogen-activated protein kinase (MAPK) pathway (A. Misawa et al., Cancer Res, 2000; 60:64-9). Our data also showed the possibility of a potent IGF-IR downstream signal cascade that accelerates progression into the S-phase, other than the MAPK pathway. In this study, we further investigated the role of this alternative pathway in the growth of neuroblastoma cells. A phosphoinositide 3-kinase (PI3K) inhibitor wortmannin blocked IGF-I-mediated induction of MycN. Our data suggest that the inhibition of MycN by wortmannin was transmitted through the MAPK pathway. Progression of the cell cycle from G1 to S phase was inhibited up to 90% by wortmannin or rapamycin, an inhibitor of mTOR, which acts downstream of PI3K. Despite its effects on induction of MycN and on progression through S phase, wortmannin did not block proliferation of neuroblastoma cells. On the other hand, rapamycin inhibited both IGF-I-induced cell cycle progression and cell proliferation in complete medium, although it had no effect on IGF-I-mediated MycN induction. Our study indicates maintenance of cell proliferation requires mTOR function, which is independent of MycN induction in human neuroblastoma cells.
AuthorsAkiko Misawa, Hajime Hosoi, Kunihiko Tsuchiya, Tohru Sugimoto
JournalInternational journal of cancer (Int J Cancer) Vol. 104 Issue 2 Pg. 233-7 (Mar 20 2003) ISSN: 0020-7136 [Print] United States
PMID12569580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2003 Wiley-Liss, Inc.
Chemical References
  • Androstadienes
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Sirolimus
  • Wortmannin
Topics
  • Androstadienes (pharmacology)
  • Cell Cycle (drug effects)
  • Cell Division (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Insulin-Like Growth Factor I (antagonists & inhibitors, pharmacology)
  • Mitogen-Activated Protein Kinases (metabolism)
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma (drug therapy, metabolism, pathology)
  • Nuclear Proteins (genetics, metabolism)
  • Oncogene Proteins (genetics, metabolism)
  • Phosphorylation (drug effects)
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins (metabolism)
  • Proto-Oncogene Proteins c-akt
  • RNA, Messenger (genetics, metabolism)
  • Sirolimus (pharmacology)
  • Time Factors
  • Tumor Cells, Cultured
  • Wortmannin

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: