@misc{10481/88201,
year = {2006},
url = {https://hdl.handle.net/10481/88201},
abstract = {The availability of oral precursors of 5-Fluorouracil (5-FU) and
its favorable results in treating advanced breast cancer have
renewed the interest in the molecular mechanisms underlying its
cytotoxicity. We have compared the changes in cell cycle and cell
death parameters induced by 2 different concentrations of 5-FU
(IC50 and IC80) in the breast adenocarcinoma cell line MCF7.
G1/S cell cycle arrest was associated with both concentrations,
whereas cell death was mainly induced after IC80 5-FU. These
changes were correlated with gene expression assessed by cDNA
microarray analysis. Main findings included an overexpression of
p53 target genes involved in cell cycle and apoptosis (CDKN1A/
p21, TP53INP, TNFRSF6/FAS and BBC3/PUMA), and significant
repression of Myc. High dose 5-FU also induced a higher regula-
tion of the mitochondrial death genes APAF1, BAK1 and BCL2,
and induction of genes of the ID family. Furthermore, we establish
a direct causal relationship between p21, ID1 and ID2 overexpres-
sion, increased acetylation of histones H3 and H4 and binding of
p53 to their promoters as a result of 5-FU treatment. The relevance
of these findings was further studied after interfering p53 expres-
sion in MCF7 cells (shp53 cells), showing a lower induction of both,
ID1 and ID2 transcripts, after 5-FU when compared with MCF7
shGFP control cells. This molecular characterization of dose- and
time-dependent modifications of gene expression after 5-FU treatment should provide a resource for future basic studies addressing
the molecular mechanisms of chemotherapy in breast cancer.},
publisher = {Wiley},
title = {Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53},
doi = {10.1002/ijc.21938},
author = {Hernandez-Vargas, Hector and Ballestar, Esteban and Carmona-Saez, Pedro and von Kobbe, Cayetano and Bañon-Rodriguez, Inmaculada and Esteller, Manel and Moreno-Bueno, Gema and Palacios, Jose and Hernandez-Vargas, Hector},
}