Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil
| Autor: | Takashi Kobunai, Masakazu Fukushima, Tatsuzo Oka, Shinji Oie, Hideki Nagase, Etsuko Sakamoto, Toshinori Oka |
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| Rok vydání: | 2007 |
| Předmět: |
Cell Survival
Orotate Phosphoribosyltransferase Biophysics Antineoplastic Agents Biology Biochemistry Thymidylate synthase Gene Expression Regulation Enzymologic Downregulation and upregulation Cell Line Tumor Neoplasms Biomarkers Tumor Dihydropyrimidine dehydrogenase medicine Humans Molecular Biology Regulation of gene expression RNA Cell Biology Molecular biology Neoplasm Proteins Gene Expression Regulation Neoplastic Fluorouracil Cell culture biology.protein Orotate phosphoribosyltransferase medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 363:216-222 |
| ISSN: | 0006-291X |
| Popis: | Although the intratumoral expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are known to affect the antitumor activity of 5-fluorouracil (5-FU), the importance of orotate phosphoribosyltransferase (OPRT) has remained unclear. This study investigated the relationship between intratumoral OPRT expression and the antitumor activity of 5-FU using human NCI60 cell lines with similar levels of TS and DPD messenger RNAs, as well as 31 tumor xenografts. The OPRT mRNA level was positively correlated with the 5-FU efficacy in these cell lines. In vitro, the 50% growth-inhibitory concentrations of 5-FU were closely correlated with the OPRT mRNA levels in cancer cell lines with similar levels of TS mRNAs when combined with a DPD inhibitor. Moreover, downregulation of OPRT with small-interfering RNA decreased the sensitivities of the cultured tumor cells to 5-FU. These results suggest that the OPRT expression level in tumors is an additional determinant of the efficacy of 5-FU. |
| Databáze: | OpenAIRE |
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