Evidence that low doses of Taxol enhance the functional transactivatory properties of p53 on p21 waf promoter in MCF-7 breast cancer cells.
In the present study, we evidence how in breast cancer cells low doses of Taxol for 18 h determined the upregulation of p53 and p21 waf expression concomitantly with a decrease of the anti-apoptotic Bcl-2. P53 and its gene product, the mdm2 protein, in treated cells exhibits a prevalent nuclear compartmentalization, thus potentiating p53 transactivatory properties. Indeed, the most important finding of this study consists with the evidence that Taxol at lower concentrations is able to produce the activation of p21 promoter via p53. Prolonged exposure of MCF-7 cells to Taxol (48 h) resulted in an increased co-association between p21 and PCNA compared to control and this well fits with the simultaneous block of cell cycle into the G2/M phase.
Panno
M Luisa
ML
Department of Cellular Biology, University of Calabria, Ponte Pietro Bucci, Cubo 4C, 87030, Arcavacata di Rende, Cosenza, Italy. mamissina@yahoo.it
Giordano
Francesca
F
Mastroianni
Fabrizia
F
Morelli
Catia
C
Brunelli
Elvira
E
Palma
M Grazia
MG
Pellegrino
Michele
M
Aquila
Saveria
S
Miglietta
Antonella
A
Mauro
Loredana
L
Bonofiglio
Daniela
D
Andò
Sebastiano
S
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D017239:Paclitaxel