AIMS: To ascertain whether the expression and enzyme activity of thymidylate synthase (TS) are related to the rapidity of cell proliferation in human cancer cell lines. METHODS: Ten asynchronously growing human cancer cell lines of different origin were used, characterised by various doubling times. TS expression was evaluated by western blot analysis using the TS 106 monoclonal antibody. TS activity was determined by the enzyme catalytic assay. The quantitative variation of TS in different phases of the cell cycle was investigated using two parameter flow cytometry for the TS protein and DNA analysis. The number of proliferating cells was evaluated by Ki67 immunostaining. RESULTS: TS expression and activity were significantly related to each other (r = 0.765; p = 0.01) and to the cell doubling time (r = -0.899; p < 0.001 and r = -0.919; p < 0.001, respectively). Ki67 immunolabelling showed no association between the number of cycling cells and TS protein expression and activity. Two parameter flow cytometry indicated that differences of TS expression in the cell lines were not related to the cell cycle phases or to the proportion of S phase cells. CONCLUSIONS: These results show that the expression and activity of the TS protein in asynchronously growing cancer cells are significantly related to the cell doubling time; the faster the cell proliferation, the greater the expression and activity of TS. These findings could explain why TS values are of prognostic value per se and why tumours with high TS expression benefit more from chemotherapy.
AIMS: To ascertain whether the expression and enzyme activity of thymidylate synthase (TS) are related to the rapidity of cell proliferation in humancancer cell lines. METHODS: Ten asynchronously growing humancancer cell lines of different origin were used, characterised by various doubling times. TS expression was evaluated by western blot analysis using the TS 106 monoclonal antibody. TS activity was determined by the enzyme catalytic assay. The quantitative variation of TS in different phases of the cell cycle was investigated using two parameter flow cytometry for the TS protein and DNA analysis. The number of proliferating cells was evaluated by Ki67 immunostaining. RESULTS:TS expression and activity were significantly related to each other (r = 0.765; p = 0.01) and to the cell doubling time (r = -0.899; p < 0.001 and r = -0.919; p < 0.001, respectively). Ki67 immunolabelling showed no association between the number of cycling cells and TS protein expression and activity. Two parameter flow cytometry indicated that differences of TS expression in the cell lines were not related to the cell cycle phases or to the proportion of S phase cells. CONCLUSIONS: These results show that the expression and activity of the TS protein in asynchronously growing cancer cells are significantly related to the cell doubling time; the faster the cell proliferation, the greater the expression and activity of TS. These findings could explain why TS values are of prognostic value per se and why tumours with high TS expression benefit more from chemotherapy.
Authors: T Takenoue; H Nagawa; K Matsuda; S Fujii; M E Nita; K Hatano; J Kitayama; T Tsuruo; T Muto Journal: Ann Surg Oncol Date: 2000-04 Impact factor: 5.344
Authors: Kirsten M L Hertoghs; Perry D Moerland; Amber van Stijn; Ester B M Remmerswaal; Sila L Yong; Pablo J E J van de Berg; S Marieke van Ham; Frank Baas; Ineke J M ten Berge; René A W van Lier Journal: J Clin Invest Date: 2010-11 Impact factor: 14.808
Authors: Linda E Kelemen; Marc T Goodman; Valerie McGuire; Mary Anne Rossing; Penelope M Webb; Martin Köbel; Hoda Anton-Culver; Jonathan Beesley; Andrew Berchuck; Sony Brar; Michael E Carney; Jenny Chang-Claude; Georgia Chenevix-Trench; Daniel W Cramer; Julie M Cunningham; Richard A Dicioccio; Jennifer A Doherty; Douglas F Easton; Zachary S Fredericksen; Brooke L Fridley; Margaret A Gates; Simon A Gayther; Aleksandra Gentry-Maharaj; Estrid Høgdall; Susanne Krüger Kjaer; Galina Lurie; Usha Menon; Patricia G Moorman; Kirsten Moysich; Roberta B Ness; Rachel T Palmieri; Celeste L Pearce; Paul D P Pharoah; Susan J Ramus; Honglin Song; Daniel O Stram; Shelley S Tworoger; David Van Den Berg; Robert A Vierkant; Shan Wang-Gohrke; Alice S Whittemore; Lynne R Wilkens; Anna H Wu; Joellen M Schildkraut; Thomas A Sellers; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-06-22 Impact factor: 4.254