Document Detail


Cytostatic effect of TNFalpha on cancer cells is independent of p21WAF1.
MedLine Citation:
PMID:  9380413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tumor necrosis factor alpha (TNFalpha) is a cytotoxic/cytostatic compound for a variety of human cancer cells. The p21WAF1 protein is a cyclin-dependent kinase inhibitor (CDKI) that binds to cyclin/cyclin-dependent kinase (CDK) complexes and inhibits their kinase activities, thereby leading to cell cycle arrest. We found that the cytostatic effect of TNFalpha on the cervical cancer cell line, ME180, was concomitant with an arrest of these cells in the G0/G1 phase of the cell-cycle. This corresponded with an increase in both p21WAF1 mRNA and protein levels which likely occurred via a p53-independent pathway since ME180 is infected with the human papilloma virus. To elucidate the role of p21WAF1 in the TNFalpha-mediated growth and cell cycle arrest, we stably transformed ME180 cells with an antisense p21WAF1 expression vector. Two clones with reduced levels of p21WAF1 both in their basal state as well as after their exposure to TNFalpha were selected. The growth of these cells was still inhibited by TNFalpha and they arrested in G0/G1 similar to wildtype or empty vector transfected cells. These results indicate that although p21WAF1 expression increases dramatically with TNFalpha treatment, it may not play a critical role in the cytostatic effect of TNFalpha on ME180 cervical cancer cells.
Authors:
M Shiohara; A F Gombart; J D Berman; K Koike; A Komiyama; H P Koeffler
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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:  15     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-11-12     Completed Date:  1997-11-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1605-9     Citation Subset:  IM    
Affiliation:
Department of Medicine, UCLA School of Medicine, Cedars-Sinai Research Institute, Los Angeles, California 90048, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle
Cell Division / drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / antagonists & inhibitors*
Cyclins / metabolism,  physiology*
Humans
RNA, Messenger / analysis
Transformation, Genetic
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / pharmacology*
Grant Support
ID/Acronym/Agency:
CA26038/CA/NCI NIH HHS; CA42710/CA/NCI NIH HHS; DK42792/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; EC 2.7.11.22/Cyclin-Dependent Kinases

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