Document Detail

Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation.
MedLine Citation:
PMID:  10030673     Owner:  NLM     Status:  MEDLINE    
The mitogen activated protein (MAP) kinases or extracellular signal-regulated kinases (Erks) are activated in response to Ras expression or exposure to tumor promoters or to growth factors, and have been implicated in AP-1 transactivation in some models. We have shown that tumor promoter induced activation of the transcription factor AP-1 is required for induced neoplastic transformation in the Balb/C JB6 cell model. Jun and Fos family protein levels have been found not to be limiting for AP-1 response. The present study asks whether activation of Erks1 and 2 is required for AP-1 transactivation and transformation of JB6 cells and whether Erks might be targeted for cancer prevention. Expression of either of two different dominant negative kinase inactive Erk2 mutants in transformation sensitive (P+) JB6 cells substantially inhibited the tumor promoter induced activation of Erks1 and 2 and of AP-1 measured by a collagenase-luciferase reporter. Multiple mutant Erk2 expressing clonal lines were also rendered non-responsive to induced neoplastic transformation. These observations, together with our recent finding attributing AP-1 non-responsiveness to Erk deficiency in a clonal line of transformation resistant (P-) cells, argue for a requirement for Erks1 and/or 2 activation in AP-1 transactivation in the mouse JB6 neoplastic progression model, and suggest the utility of Erks as a prevention target.
R G Watts; C Huang; M R Young; J J Li; Z Dong; W D Pennie; N H Colburn
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncogene     Volume:  17     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-03-12     Completed Date:  1999-03-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  3493-8     Citation Subset:  IM    
National Cancer Institute-FCRDC, Laboratory of Biochemical Physiology, Frederick, Maryland 21702-1201, USA.
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MeSH Terms
Calcium-Calmodulin-Dependent Protein Kinases / drug effects,  genetics,  metabolism*
Carcinogens / pharmacology
Cell Line / drug effects,  metabolism
Cell Transformation, Neoplastic / genetics*
Epidermal Growth Factor / pharmacology
Epidermis / cytology
Gene Expression Regulation, Neoplastic
Genes, Dominant*
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases*
Recombinant Proteins / genetics,  metabolism
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factor AP-1 / drug effects,  genetics*,  metabolism
Transcriptional Activation / genetics*
Reg. No./Substance:
0/Carcinogens; 0/Recombinant Proteins; 0/Transcription Factor AP-1; 16561-29-8/Tetradecanoylphorbol Acetate; 62229-50-9/Epidermal Growth Factor; EC Protein Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases

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