RT Journal Article
SR Electronic
T1 5-Fluorouracil: Identification of Novel Downstream Mediators of Tumour Response
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 417
OP 424
VO 24
IS 2A
A1 JOHN BOYER
A1 PAMELA J. MAXWELL
A1 DANIEL B. LONGLEY
A1 PATRICK G. JOHNSTON
YR 2004
UL http://ar.iiarjournals.org/content/24/2A/417.abstract
AB Background: 5-Fluorouracil (5-FU) is routinely used in the treatment of gastrointestinal, breast and head and neck cancers. A major limitation to the use of this drug is acquired or inherent resistance. Materials and Methods: To examine the downstream molecular signals activated in response to 5-FU, we used DNA microarray technology to examine global transcriptional changes in 5-FU-treated MCF-7 breast cancer cells. Results: We identified several novel 5-FU-inducible target genes that have not previously been linked to 5-FU response, including spermine/spermidine acetyl transferase (SSAT) and annexin II. Treatment of MCF-7 cells with the antifolate tomudex (TDX) and the DNA damaging agent oxaliplatin also caused up-regulation of each target gene. Inactivation of wild-type p53 abrogated the 5-FU-mediated induction of SSAT and annexin II. Inducible expression of thymidylate synthase completely abrogated TDX-, but not 5-FU-mediated induction of each gene. Furthermore, basal expression of SSAT and annexin II was elevated in cells resistant to 5-FU. Conclusion: These data demonstrate the potential of microarray analysis to identify novel genes associated with response or resistance to chemotherapeutic agents. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved