Document Detail


R-Ras promotes tumor growth of cervical epithelial cells.
MedLine Citation:
PMID:  12548599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: R-Ras is 55% identical to H-Ras. However, these two oncogenes seem to have different tumor-transforming potential. R-Ras induced cell transformation in fibroblasts but not in other cell types. R-Ras also reportedly induces a more invasive phenotype in breast epithelial cells through integrin activation. The authors studied the mechanisms whereby R-Ras induces a malignant phenotype. METHODS: Dominant negative (R-Ras43N) and constitutively active (R-Ras87L) mutants of R-Ras were stably transfected into human cervical epithelium C33A cells. Transfected cells were analyzed for adhesion, cell spreading, migration, and growth in culture and in nude mice. The activity of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-K) also was determined by Western blot analysis and by in vitro kinase assays. RESULTS: R-Ras87L-transfected cells, but not R-Ras43 N-transfected cells, had a higher growth rate in nude mice and in culture compared with control cells. None of the transfected C33A cells showed an increase in cell adhesion to fibronectin or collagen I, nor did they show an increment of beta1 integrin affinity. However, cells that expressed R-Ras87L, but not cells that expressed R-Ras 43N, presented a marked increase in cell spreading and migration through collagen-coated membranes. Increases in cell proliferation, spreading, and migration induced by R-Ras87L were inhibited by the PI 3-K inhibitor LY294002. In addition, PI 3-K activity, but not ERK activity, was increased only in cells that expressed R-Ras87L. CONCLUSIONS: These data suggest that the oncogene R-Ras promotes tumor growth of cervical epithelial cells and increases their migration potential over collagen through a pathway that involves PI 3-K.
Authors:
Héctor Rincón-Arano; Ricardo Rosales; Nancy Mora; Armando Rodriguez-Castañeda; Carlos Rosales
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer     Volume:  97     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-27     Completed Date:  2003-02-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  575-85     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11093
Affiliation:
Immunology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase
Animals
Cell Adhesion
Cell Cycle
Cell Division / genetics*
Cell Line, Transformed
Cell Movement / genetics*
Cell Transformation, Neoplastic / genetics*
Cervix Uteri / cytology*
Collagen
Epithelial Cells / cytology
Female
Fibronectins
GTP Phosphohydrolases
Genes, ras* / genetics
Humans
Mice
Mice, Nude
Mitogen-Activated Protein Kinases
Oncogene Proteins
Signal Transduction
Transfection
Uterine Cervical Neoplasms / pathology*
ras Proteins
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Oncogene Proteins; 9007-34-5/Collagen; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.6.1.-/GTP Phosphohydrolases; EC 3.6.1.-/RRAS protein, human; EC 3.6.1.-/Rras protein, mouse; EC 3.6.5.2/ras Proteins

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


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