Document Detail


p53, secreted by K-Ras-Snail pathway, is endocytosed by K-Ras-mutated cells; implication of target-specific drug delivery and early diagnostic marker.
MedLine Citation:
PMID:  19347028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p53 is eliminated from K-Ras-mutated cancer cells through direct interaction with Snail. However, it is not achieved through proteasome-mediated degradation or transcriptional repression. Here we provide evidence that p53, binding with Snail, is exported from a K-Ras-mutated cell through a vesicle transport-like mechanism, independently using a p53-nuclear-exporting mechanism. Although we can detect p53 in culture media, a majority of p53 might be degraded by extracellular proteases. Thus, we can recover the secreted p53 in culture media by the inhibition of protease and endocytosis. In addition, a considerable amount of p53 is endocytosed by neighboring cells. As p53 resorption occurs in a K-Ras-dependent manner, treatment of recombinant p53 is detected in the whole-cell lysate of K-Ras-mutated cells, but not in that of wild-type cells. Using the property of p53, we can deliver the chemical (propidium iodine) into K-Ras mutated cells selectively. In contrast, Snail, a co-secreted protein with p53 in response to oncogenic K-Ras, shows resistance to endocytosis and protease, and results in remaining in the media. Thus, we can detect an autoantibody against Snail in the serum of a human cancer patient. Our finding can be used for a mutant K-Ras-specific anticancer drug delivery system and for the diagnosis of pancreatic, colon and lung cancers.
Authors:
S-H Lee; S-J Lee; J-Y Chung; Y-S Jung; S-Y Choi; S H Hwang; D Choi; N-C Ha; B-J Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-06
Journal Detail:
Title:  Oncogene     Volume:  28     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-14     Completed Date:  2009-05-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  2005-14     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Pusan National University, Busan, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Autoantibodies / analysis
Drug Delivery Systems
Humans
Neoplasms / drug therapy,  metabolism*
Signal Transduction
Transcription Factors / metabolism*
Transport Vesicles / metabolism
Tumor Suppressor Protein p53 / analysis,  genetics,  metabolism*
ras Proteins / metabolism*
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/snail family transcription factors; EC 3.6.5.2/ras Proteins

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