In this study, we demonstrated for the first time, that human TS and DHFR form a strong complex in vitro and co-localize in human normal and colon cancer cell cytoplasm and nucleus.
EMAST was more frequent in colon cancer than rectal cancer (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3 (p=0.004), and overexpression of thymidylate synthase (p=0.006).
Here, we demonstrate that the enhanced HSP90 function and subsequent activation of Src induce expression of TYMS and acquired resistance to 5-FU in colon cancer.
Regulation of TS by irinotecan was evaluated by western blotting and quantitative real-time PCR assay. dMMR accounted for 18.5 % and was related with proximal colon cancer (p = 0.005), poorly differentiated tumors (p = 0.018) and favorable efficacy with a higher disease control rate (DCR), a longer progression-free survival (PFS) and a trend of longer overall survival (OS). dMMR colon cancer cells were more sensitive to irinotecan.
In the present study, AQP5 and P-glycoprotein (P-gp), glutathione S-transferase-π (GST-π), topoisomerase II (TOPO II), and thymidylate synthase (TS) were checked in CC and adjacent cancer tissues; AQP5-siRNA was applied to silencing AQP5 in CC cell line HT-29, 5-fluorouracil (5-FU), and cisplatin (DDP) added on cells, and sulforhodamine B (SRB) was used; fluorescence real-time quantitative RT-PCR and Western blot were employed to detect changes in multidrug resistance factor and expression mitogen-activated protein kinase (MAPK) signaling pathway in HT-29.
These features include cellular morphology, expression of colon cancer stem cell markers, expression of survivin and thymidylate synthase and sensitivity to fluorouracil.
This study evaluates if a combined analysis of MMR status and TS expression in colon cancer can add prognostic value and better predict response to adjuvant 5-FU-based chemotherapy.
We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL.
Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences.
Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences.
In this study, we demonstrate that the histone deacetylase inhibitors (HDACi) vorinostat and LBH589 significantly downregulate TS gene expression in a panel of colon cancer cell lines.
In this study, a comprehensive gene expression analysis at the levels of both transcriptional and post-transcriptional regulation was conducted to identify response markers using human genome array with TS-depleted human colon cancer HCT-C18 (TS-) cells and HCT-C18 (TS+) cells stably transfected with the human TS cDNA expression plasmid.
MSI status and TS expression were unrelated and TS was not prognostic, suggesting that TS levels cannot explain therapeutic resistance to 5-FU reported in MSI-H colon cancers.