Document Detail


Adenovirus-mediated p16/CDKN2 gene transfer induces growth arrest and modifies the transformed phenotype of glioma cells.
MedLine Citation:
PMID:  8552379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The p16 (MTS1/CDKN2) gene localized at the 9p21 chromosomal region encodes for a cell cycle inhibitor protein and is altered in many human cancers. The frequency of p16 alterations in gliomas exceeds 50%. To restore the missing wild-type p16 gene efficiently in glioma cells an adenovirus vector carrying the full length coding sequence of the wild-type p16 cDNA, Ad5RSV-p16, was constructed. Three human glioma cell lines, U251 MG, U-87 MG and D54 MG, that did not express endogenous p16/CDKN2 gene and were easily infected with adenovirus vectors were selected for these experiments. Introduction of the Ad5RSV-p16 in these malignant glioma cell lines directed the biosynthesis of functional p16 protein in the majority of the exposed cells, significantly inhibited cell growth, influenced cell morphology and modified the transformed phenotype of cells including the ability to form colonies in soft agar. Flow cytometric studies revealed that the majority of the Ad5RSV-p16 infected glioma cells were arrested in the G0-G1 phases of the cell cycle. These results suggest that p16/CDKN2 inactivation is a significant factor in the genesis and progression of gliomas and that the restoration of the wild-type p16 protein could have clinical and therapeutic utility.
Authors:
J Fueyo; C Gomez-Manzano; W K Yung; G L Clayman; T J Liu; J Bruner; V A Levin; A P Kyritsis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  12     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1996 Jan 
Date Detail:
Created Date:  1996-02-20     Completed Date:  1996-02-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  103-10     Citation Subset:  IM    
Affiliation:
Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Carrier Proteins / genetics*
Cell Division
Cell Transformation, Neoplastic
Cyclin-Dependent Kinase Inhibitor p16
Gene Therapy*
Gene Transfer Techniques
Genes, Tumor Suppressor*
Glioma / therapy*
Humans
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
P01-CA55261/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16

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


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