Thymidylate synthase expression and activity: relation to S-phase parameters and 5-fluorouracil sensitivity.
Fiche publication
Date publication
juillet 1998
Journal
British journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel, Pr MERLIN Jean-Louis
Tous les auteurs :
Mirjolet JF, Barberi-Heyob M, Merlin JL, Marchal S, Etienne MC, Milano G, Bey P
Lien Pubmed
Résumé
Six human cancer cell lines exhibiting a large range of sensitivity to 5-fluorouracil (5-FU) were evaluated for thymidylate synthase (TS) and p53 gene expression, TS and dihydropyrimidine dehydrogenase (DPD) activity, as well as cell cycle parameters, S-phase fraction (SPF), bromodeoxyuridine labelling index (LI) and S-phase duration (SPD). All these parameters were investigated for 7 days in asynchronously growing cell populations and compared with the cell sensitivity to 5-FU. No significant correlation was found between S-phase parameters and TS gene expression and/or activity. TS activity was higher in proliferating cells; however, it was not significantly higher in rapidly growing cell lines with short SPD. Neither TS gene expression nor activity was found to correlate with 5-FU sensitivity. On the another hand, a statistically significant correlation (P < 0.0001) was observed between LI and SPD and 5-FU sensitivity. The present results suggest that cell cycle parameters such as SPD and/or LI could be better parameters for 5-FU sensitivity prediction than TS gene expression and/or activity. This could be especially informative in cases of concomitant radio-chemotherapy as S-phase parameters are already proposed for hyperfractionated radiotherapy planning.
Mots clés
Antimetabolites, Antineoplastic, pharmacology, Cell Division, drug effects, Dihydrouracil Dehydrogenase (NADP), Fluorouracil, pharmacology, Gene Expression Regulation, Enzymologic, Humans, Neoplasm Proteins, genetics, Oxidoreductases, metabolism, S Phase, physiology, Thymidylate Synthase, genetics, Tumor Cells, Cultured, drug effects
Référence
Br. J. Cancer. 1998 Jul;78(1):62-8