Document Detail


Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells.
MedLine Citation:
PMID:  10412049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lactoferrin inhibits cell proliferation and suppresses tumor growth in vivo. However, the molecular mechanisms underlying these effects remain unknown. In this in vitro study, we demonstrate that treatment of breast carcinoma cells MDA-MB-231 with human lactoferrin induces growth arrest at the G1 to S transition of the cell cycle. This G1 arrest is associated with a dramatic decrease in the protein levels of Cdk2 and cyclin E correlated with an inhibition of the Cdk2 kinase activity. Cdk4 activity is also significantly decreased in the treated cells and is accompanied by an increased expression of the Cdk inhibitor p21(CIP1). Furthermore, we show that lactoferrin maintains the cell cycle progression regulator retinoblastoma protein pRb in a hypophosphorylated form. Additional experiments with synchronized cells by serum depletion confirm the anti-proliferative activity of human lactoferrin. These effects of lactoferrin occur through a p53-independent mechanism both in MDA-MB-231 cells and other epithelial cell lines such as HBL-100, MCF-7, and HT-29. These findings demonstrate that lactoferrin induces growth arrest by modulating the expression and the activity of key G1 regulatory proteins.
Authors:
E Damiens; I El Yazidi; J Mazurier; I Duthille; G Spik; Y Boilly-Marer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  74     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-09-27     Completed Date:  1999-09-27     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  486-98     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Wiley-Liss, Inc.
Affiliation:
Laboratoire de Chimie Biologique, Unité Mixte de Recherche du CNRS no 8576, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / metabolism*,  pathology
CDC2-CDC28 Kinases*
Cell Cycle / physiology
Cell Cycle Proteins*
Cell Division
Colonic Neoplasms / metabolism
Cyclin E / metabolism
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases / antagonists & inhibitors*,  metabolism
Cyclins / metabolism
Dose-Response Relationship, Drug
G1 Phase*
Humans
Lactoferrin / pharmacology*
Microtubule-Associated Proteins / metabolism
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins*
Thymidine / metabolism
Time Factors
Tumor Cells, Cultured
Tumor Suppressor Proteins*
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Microtubule-Associated Proteins; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 50-89-5/Thymidine; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.4.21.-/Lactoferrin

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