Document Detail

Differential gene expression in p53-mediated apoptosis-resistant vs. apoptosis-sensitive tumor cell lines.
MedLine Citation:
PMID:  11069295     Owner:  NLM     Status:  MEDLINE    
Induction of wild-type p53 in the ECV-304 bladder carcinoma cell line by infection with a p53 recombinant adenovirus (Ad5CMV-p53) resulted in extensive apoptosis and eventual death of nearly all of the cells. As a strategy to determine the molecular events important to p53-mediated apoptosis in these transformed cells, ECV-304 cells were selected for resistance to p53 by repeated infections with Ad5CMV-p53. We compared the expression of 5,730 genes in p53-resistant (DECV) and p53-sensitive ECV-304 cells by reverse transcription-PCR, Northern blotting, and DNA microarray analysis. The expression of 480 genes differed by 2-fold or more between the two p53-infected cell lines. A number of potential targets for p53 were identified that play roles in cell cycle regulation, DNA repair, redox control, cell adhesion, apoptosis, and differentiation. Proline oxidase, a mitochondrial enzyme involved in the proline/pyrroline-5-carboxylate redox cycle, was up-regulated by p53 in ECV but not in DECV cells. Pyrroline-5-carboxylate (P5C), a proline-derived metabolite generated by proline oxidase, inhibited the proliferation and survival of ECV-304 and DECV cells and induced apoptosis in both cell lines. A recombinant proline oxidase protein tagged with a green fluorescent protein at the amino terminus localized to mitochondria and induced apoptosis in p53-null H1299 non-small cell lung carcinoma cells. The results directly implicate proline oxidase and the proline/P5C pathway in p53-induced growth suppression and apoptosis.
S A Maxwell; G E Davis
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  97     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-12     Completed Date:  2001-05-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  13009-14     Citation Subset:  IM    
Department of Pathology and Laboratory Medicine, Texas A&M University Health Science Center, College Station, TX 77843-1114, USA.
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MeSH Terms
Apoptosis / physiology*
Arginase / genetics
Drug Resistance, Multiple*
Galactosidases / genetics
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic*
Genetic Vectors
Green Fluorescent Proteins
Luminescent Proteins / genetics
Oligonucleotide Array Sequence Analysis
Proline Oxidase / genetics
Recombinant Proteins / analysis
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism*
Urinary Bladder Neoplasms
Grant Support
Reg. No./Substance:
0/Luminescent Proteins; 0/Recombinant Proteins; 0/Tumor Suppressor Protein p53; 147336-22-9/Green Fluorescent Proteins; EC 1.5.3.-/Proline Oxidase; EC 3.2.1.-/Galactosidases; EC

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