Document Detail


Discordant effects of rapamycin on proliferation and p70S6 kinase phosphorylation in normal and neoplastic rat chromaffin cells.
MedLine Citation:
PMID:  10025577     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Normal adult rat chromaffin cells show a robust proliferative response in vitro to nerve growth factor (NGF) and other mitogens. In contrast, PC12 rat pheochromocytoma cells proliferate in the absence of exogenous mitogens and undergo neuronal differentiation in response to NGF. We demonstrate in this work that the antiproliferative drug rapamycin suppresses normal chromaffin cell proliferation. This effect is blocked by FK 506, indicating that it occurs via interaction of rapamycin with its intracellular binding protein, FKBP. Rapamycin must be added within 2 days of mitogen stimulation in order to be fully effective. PC12 cells are refractory to the antiproliferative effect of rapamycin, although rapamycin does exert its expected inhibitory effect in PC12 cells on both basal and NGF-stimulated activation of one of its biochemical targets, the 70-kDa S6 protein kinase (p70S6K). The discordant findings suggest that a proliferative signal normally requiring activation of p70S6K either is unnecessary in PC12 cells or is provided by a downstream or cross-communicating pathway. They also suggest that p70S6K does not participate in the morphological responses of PC12 cells to NGF. Determining the basis for rapamycin resistance in PC12 cells might help to identify signaling abnormalities involved in the pathogenesis of pheochromocytoma.
Authors:
J F Powers; A S Tischler; V Cherington
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroscience letters     Volume:  259     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-05-24     Completed Date:  1999-05-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  137-40     Citation Subset:  IM    
Affiliation:
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division / drug effects
Chromaffin Cells / cytology,  drug effects*,  enzymology
Female
Immunosuppressive Agents / pharmacology*
PC12 Cells / cytology,  drug effects*
Phosphorylation / drug effects
Rats
Rats, Inbred F344
Ribosomal Protein S6 Kinases / drug effects*,  metabolism
Sirolimus / pharmacology*
Tacrolimus / pharmacology
Grant Support
ID/Acronym/Agency:
CA48017/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 109581-93-3/Tacrolimus; 53123-88-9/Sirolimus; EC 2.7.11.1/Ribosomal Protein S6 Kinases

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