Normal breast epithelial cells induce apoptosis of MCF-7 breast cancer cells through a p53-mediated pathway.
Cancer development depends not only on the nature of the tumor cells themselves but also on the regulatory effects of various normal cells. The present study was performed to better understand the mechanism by which normal breast epithelial cells (NBEC) can control the growth of MCF-7 breast cancer cells. When MCF-7 cells were treated with NBEC conditioned medium, cell growth was inhibited in a concentration-dependent manner. This inhibition was due to an induction of apoptosis without any change in cell cycle progression. The induction of apoptosis was correlated with increased levels of p53, p21(waf1) and decreased levels of bcl-2. Transient transfections of MCF-7 cells with two p53 cDNA constructs demonstrated the induction of apoptosis was mediated by endogenous p53. Taken together, our results indicate that NBEC inhibit the growth of MCF-7 breast cancer cells by inducing apoptosis in them via endogenous p53.
Toillon
R A
RA
Laboratoire de Biologie du Développement, Equipe Facteurs de Croissance (UPRES 1033), Villeneuve d'Ascq Cedex, 59655, France.
Adriaenssens
E
E
Wouters
D
D
Lottin
S
S
Boilly
B
B
Hondermarck
H
H
Bourhis
X L
XL
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C493956:CDKN1A protein, human; D017077:Culture Media, Conditioned; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein