Document Detail

Local regulation of homeostasis favors chromosomal instability.
MedLine Citation:
PMID:  12676089     Owner:  NLM     Status:  MEDLINE    
Tissues of long-lived multicellular organisms have to maintain a constant number of functioning cells for many years. This process is called homeostasis. Homeostasis breaks down when cells emerge with mutations in tumor suppressor genes or oncogenes. Such mutated cells can have increased net rates of proliferation, which is increased somatic fitness. We show that the best protection against such mutations is achieved when homeostasis is regulated locally via small compartments. Small compartments, on the other hand, allow the accumulation of cells with reduced somatic fitness. Cells with mutations conferring genetic instability normally have a reduced somatic fitness because they have an increased probability of producing deleterious mutations or triggering apoptosis. Thus, small compartments protect against mutations in tumor suppressor genes or oncogenes but promote the emergence of genetic instability.
Franziska Michor; Yoh Iwasa; Natalia L Komarova; Martin A Nowak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current biology : CB     Volume:  13     ISSN:  0960-9822     ISO Abbreviation:  Curr. Biol.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-04     Completed Date:  2003-12-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  581-4     Citation Subset:  IM    
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
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MeSH Terms
Cell Transformation, Neoplastic / genetics
Chromosome Disorders / genetics*
Genes, Tumor Suppressor / physiology*
Homeostasis / genetics*,  physiology*
Loss of Heterozygosity / genetics
Models, Genetic
Models, Theoretical
Mutation / genetics*,  physiology
Oncogenes / genetics,  physiology*

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