Document Detail

Differential induction of c-fos and c-jun proto-oncogenes and AP-1 activity by tumor promoter 12-O-tetradecanoyl phorbol 13-acetate in cells at different stages of tumor promotion in vitro.
MedLine Citation:
PMID:  1437150     Owner:  NLM     Status:  MEDLINE    
A two-stage (initiation and promotion) model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the molecular mechanisms of tumor promotion in vitro. C3H10T1/2 cells which had been initiated with a subcarcinogenic dose (0.5 micrograms ml-1) of benzo[a]pyrene (B[a]P) were isolated after 12-O-tetradecanoyl phorbol 13-acetate (TPA) treatment lasting 12, 24 or 36 days. These series of partially promoted cells were designated T-12, T-24 and T-36 cells. T-12 and T-24 cells exhibited higher anchorage-independent growth on soft agar in the presence of TPA than did the initiated or T-36 cells. Cytosolic protein kinase C (PKC) in the resting state was slightly depleted in T-24 and T-36 cells. Proteolytic down-regulation of membrane-bound PKC was enhanced in T-12 cells compared with the initiated cells after 3 h of TPA treatment. Induction of c-fos and c-jun proto-oncogene expression increased two- to threefold in T-12 cells. Moreover, the basal level of c-fos mRNA progressively increased in T-12, T-24 and T-36 cells. As compared with other cell types, T-12 cells had the highest AP-1 DNA-binding activity at both the basal level and at 30 min after TPA treatment. These results indicate that deregulation of the TPA-induced cellular responses occurs in the cells at various stages of tumor promotion, and might be associated with transforming processes.
W S Wu; J K Lin; F Y Wu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  7     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-12-08     Completed Date:  1992-12-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2287-94     Citation Subset:  IM    
Institute of Biomedical Sciences (IBMS), Academia Sinica, Taipei, Taiwan, ROC.
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MeSH Terms
Base Sequence
Cell Transformation, Neoplastic / drug effects*
Cells, Cultured
DNA / metabolism
Gene Expression Regulation*
Genes, fos*
Molecular Sequence Data
Protein Kinase C / analysis
Proto-Oncogene Proteins c-fos / biosynthesis
Proto-Oncogene Proteins c-jun / biosynthesis*,  genetics
Tetradecanoylphorbol Acetate / pharmacology*
Reg. No./Substance:
0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 16561-29-8/Tetradecanoylphorbol Acetate; 9007-49-2/DNA; EC Kinase C

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