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.
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.
TS mRNA expression determined by real-time reverse transcription-PCR correlated with TS protein levels determined by TS immunoblot and immunohistochemistry in cultured colon cancer cell lines and paraffin-embedded primary tumor tissue.
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.
Recently, it has become apparent that rTSb overexpression can cause the downregulation of TS protein in a colon cancer cell line through the production of > or = 1 previously unknown signaling molecules.
We investigated on colon cancer cells the effect of geraniol on thymidylate synthase and thymidine kinase expression, two enzymes related to 5-fluorouracil cytotoxicity.
Transfection of TS1058 siRNA into human colon cancer RKO cells resulted in a dose-dependent inhibition of TS expression with an IC(50) value of 10 pM but had no effect on the expression of alpha-tubulin or topoisomerase I. Inhibition of TS expression by TS1058 was maximal at 48 h and remained suppressed for up to 5 days.
Polymorphism of the thymidylate synthase gene and thymidylate synthase levels in colon cancer cell lines and different tissues of colorectal cancer patients.
The functional significance of a transfected K-Ras oncogene in influencing apoptosis induced by thymineless stress was examined in a thymidylate synthase (TS)-deficient (TS-) colon carcinoma cell line derived from GC3/c1 after thymidine deprivation.
In thymidylate synthase-deficient (TS-) colon carcinoma cells, thymineless death is mediated via Fas/Fas ligand (FasL) interactions after thymidine deprivation and inhibited by the Fas-inhibitory monoclonal antibody NOK-1.
These features include cellular morphology, expression of colon cancer stem cell markers, expression of survivin and thymidylate synthase and sensitivity to fluorouracil.
Cell death due to thymine (dThd) deficiency, associated with the cytotoxic action of 5-fluorouracil in colon cancer, is regulated in thymidylate synthase-deficient (TS(-)) human colon carcinoma cells via the Fas (CD95, APO-1) death receptor.
We recently reported that activation of CaSR in human colon carcinoma cells downregulated the expression of thymidylate synthase (TS) and survivin and promoted a significant increase in sensitivity to cytotoxic drugs.