[The correlation between thymidylate synthase expression and cytotoxicity of 5-fluorouracil in human cancer cell lines: study using polyclonal antibody against recombinant human thymidylate synthase].
To estimate the relationship between the expression of thymidylate synthase (TS) in tumors and clinical response and prognosis in cancer patients treated with 5-fluorouracil (5-FU), the anti-TS polyclonal antibody against recombinant human TS (rhTS) was prepared and purified. At the initial stage, we attempted to clarify the relationships between the expression of TS protein and the cytotoxicity of 5-FU in established human cancer cells in vitro. Our purified anti-TS antibody was demonstrated to react specifically with intracellular TS as revealed by western blot analysis and immunohistochemistry. Furthermore, it was revealed that the expression of TS proteins correlated with cytotoxicity (IC50 value) of 5-FU against human colorectal tumor cells, both sensitive and those with acquired resistance to 5-fluoropyrimidines, and other cancer cell lines as well. These results suggest that our anti-TS polyclonal antibody (IgG) is suitable for clinical prospective and retrospective studies on TS expression in various cancers as a prognostic factor and 5-FU response-predicting parameter.
Okabe
H
H
Second Cancer Research Laboratory, Taiho Pharmaceutical Co., Ltd.
Tsujimoto
H
H
Fukushima
M
M
D000906:Antibodies / Q000276:immunology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013940:Thymidylate Synthase / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000906:Antibodies; D000964:Antimetabolites, Antineoplastic; D011994:Recombinant Proteins; D013940:Thymidylate Synthase; D005472:Fluorouracil