Document Detail


Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle.
MedLine Citation:
PMID:  8196666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The proto-oncogene transcription factors Fos and Jun form a heterodimeric complex that binds to DNA and regulates expression of specific target genes. Continuous expression of c-fos causes transformation of cultured fibroblasts and induces osteogenic sarcoma in mice. To investigate the molecular basis of fos-mediated oncogenesis, we developed a conditional cell transformation system in which Fos expression was regulated by isopropyl-beta-D-thiogalactopyranoside (IPTG). Synthesis or repression of Fos in L1-3c-fos cells occurred rapidly, within 30 min, after the removal or addition of IPTG to the culture medium. However, there was a significant delay between the induction of Fos expression and the appearance of morphological transformation. No effect was observed after 12 h of Fos expression, partial transformation was detected after 24 h, and full transformation required approximately 3 days of continuous Fos expression. Similarly, the transformed cell morphology persisted for at least 2 days after repression of Fos, and a normal phenotype was observed only after 3 days. Fos-Jun complexes, capable of binding to AP-1 sequences, were present continuously during the delay in morphological transformation. Furthermore, increased expression of several candidate Fos target genes, including those encoding Fra-1, transin (stromelysin), collagenase, and ornithine decarboxylase, was detected shortly after Fos induction. The induction of morphological transformation was not dependent on the cell cycle, as it occurred in both cycling and noncycling cells. Thus, the Fos-Jun complexes present before L1-3c-fos cells become fully transformed are transcriptionally active. These complexes disappeared, and the Fos target genes were repressed at least 2 days prior to reversion. Our results suggest that cell transformation by Fos requires increased expression of a target gene(s) with a long-lived product(s) that must reach a critical level.
Authors:
G G Miao; T Curran
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  14     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-06-24     Completed Date:  1994-06-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4295-310     Citation Subset:  IM    
Affiliation:
Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Neoplasms / genetics
Cell Cycle / drug effects,  physiology*
Cell Division / drug effects,  physiology
Cell Transformation, Neoplastic*
Cells, Cultured
DNA-Binding Proteins / metabolism
Fibroblasts
Gene Expression* / drug effects
Genes, fos*
Isopropyl Thiogalactoside / pharmacology
Kinetics
Mice
Osteosarcoma / genetics
Proto-Oncogene Proteins c-fos / biosynthesis*,  metabolism
Proto-Oncogene Proteins c-jun / metabolism
Restriction Mapping
Time Factors
Transfection
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 367-93-1/Isopropyl Thiogalactoside
Comments/Corrections

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