Document Detail

The role of Rac1 in maintaining malignant phenotype of mouse skin tumor cells.
MedLine Citation:
PMID:  15893875     Owner:  NLM     Status:  MEDLINE    
We have previously developed an in vitro tumor progression model with mouse skin keratinocytes to study the molecular targets that mediate the tumor cell's progression from a benign to a malignant phenotype. The malignantly transformed cells were found to have elevated MAP kinase signaling and increases in AP-1, NFkappaB and cAMP response element (CRE) transcription factors activities compared to their benign counter-part. In this study, we showed that Rac1, a member of the Rho superfamily of small GTPases, functions as a key signaling molecule that mediates these malignant phenotypes. We used a doxycycline inducible system to express dominant negative Rac1 (N17 Rac1) in the squamous cell carcinomas producing 6M90 cell line. Conditional expression of the N17 Rac1 was able to decrease multiple markers of malignancy including: growth rate, colony formation, migration, invasion and most importantly, in vivo tumor growth. In addition, these phenotypic changes were accompanied by decreases in mitogenic signals, which include ERK1/2, JNK, and PI-3 kinase/Akt activation. Transactivation mediated by AP-1, NFkappaB, and CRE were also attenuated by expression of dominant negative Rac1. These observations led us to conclude that Rac1 signaling is required for the malignant phenotypes of the squamous cell carcinoma cells.
Kevin A Kwei; Joanne S Finch; James Ranger-Moore; G Tim Bowden
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer letters     Volume:  231     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-09     Completed Date:  2006-03-09     Revised Date:  2014-02-07    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  326-38     Citation Subset:  IM    
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Blotting, Western
Carcinoma, Squamous Cell / metabolism,  pathology,  prevention & control
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic*
Colony-Forming Units Assay
Cyclic AMP Response Element-Binding Protein / metabolism
Doxycycline / pharmacology
Genes, Dominant
MAP Kinase Kinase 4 / metabolism
Mice, SCID
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
NF-kappa B / genetics,  metabolism
Neoplasm Invasiveness
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction*
Skin Neoplasms / metabolism*,  pathology*,  prevention & control
Survival Rate
Transcription Factor AP-1 / metabolism
Transcriptional Activation
rac1 GTP-Binding Protein / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Cyclic AMP Response Element-Binding Protein; 0/NF-kappa B; 0/Transcription Factor AP-1; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt; EC Protein Kinase 1; EC Protein Kinase 3; EC Kinase Kinase 4; EC GTP-Binding Protein; N12000U13O/Doxycycline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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