5-Fluorouracil Induction of Fas and Apoptosis in Colon Cancer Patients: Relation of Clinical Outcome with Thymidylate Synthase, Mcl-1 and Rb View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2002

AUTHORS

G. J. Peters , H. H. J. Backus , D. F. Dukers , C. J. Van Groeningen , W. Vos , E Bloemena , D. Wouters , J. M. G. H. Van Riel , K. Smid , H. M. Pinedo

ABSTRACT

Thymidylate synthase (TS), catalyses the methylation of dUMP to dTMP with 5,10-methylene-tetrahydrofolate (CH2-THF) (1, 2). The active metabolite of 5-fluorouracil (5-FU), FdUMP forms a ternary complex with TS and CH2-THF leading to TS inhibition, growth arrest and cell death (1), which is stimulated by leucovorin (LV) (3, 4). Resistance to 5-FU is not only related to high TS levels, but also to mechanisms involved in cell growth inhibition or programmed cell death (3, 4, 5). Cell cycle progression is controlled by p53 (6), p21 (7), Rb and E2F (8). Drug treatment induces DNA damage, and p53 activates p21 to initiate cell cycle arrest. The tumor suppressor gene Rb forms a complex with E2F inhibiting their transcriptional activity (8). After phosphorylation of Rb by specific kinases, cell cycle progression can be activated by release of E2F1 and E2F2. More... »

PAGES

461-466

References to SciGraph publications

Book

TITLE

Chemistry and Biology of Pteridines and Folates

ISBN

978-1-4613-5317-1
978-1-4615-0945-5

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-1-4615-0945-5_78

DOI

http://dx.doi.org/10.1007/978-1-4615-0945-5_78

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019282731


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