Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil.

Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. Research Abstract Details 

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Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. Abstract Text:

Etsuko Sakamoto,Hideki Nagase,Takashi Kobunai,Shinji Oie,Toshinori Oka,Masakazu Fukushima,Tatsuzo Oka,Etsuko Sakamoto,Hideki Nagase,Takashi Kobunai,Shinji Oie,Toshinori Oka,Masakazu Fukushima,Tatsuzo Oka,

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.

Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. Publishing Authors By Initials

E Sakamoto,H Nagase,T Kobunai,S Oie,T Oka,M Fukushima,T Oka,E Sakamoto,H Nagase,T Kobunai,S Oie,T Oka,M Fukushima,T Oka,

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Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemical and biophysical research communication

VOLUME: 363

Page Numbers: 216-22

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 0006-291X

DAY: 6

MONTH: 09

YEAR: 2007

Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. Information

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LANGUAGE: eng

NlmUniqueID: 372516

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AFFILIATION: Personalized Medicine Research Laboratory, Taiho Pharmaceutical Co., Ltd., 224-2 Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan. etsu-toda@taiho.co.jp

Country: United States

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MEDLINETA: Biochem Biophys Res Commun

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