Influence of 5-fluorouracil on ferredoxin reductase mRNA splice variants in colorectal carcinomas

Schneider,Mark; Tanaka-Nozaki,Motoko; Kato,Shunji; Blömeke,Brunhilde

doi:10.3892/ol_00000062

March-April 2010 Volume 1 Issue 2

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March-April 2010 Volume 1 Issue 2

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Article

Influence of 5-fluorouracil on ferredoxin reductase mRNA splice variants in colorectal carcinomas

Authors:
- Mark Schneider
- Motoko Tanaka-Nozaki
- Shunji Kato
- Brunhilde Blömeke
View Affiliations / Copyright

Affiliations: Department of Environmental Toxicology, University of Trier, 54296 Trier, Germany
Pages: 351-354
|
Published online on: March 1, 2010

https://doi.org/10.3892/ol_00000062
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Abstract

5-Fluorouracil (5-FU) is a frequently used antitumor drug. Recently, it has been shown that mRNA and protein levels of the ferredoxin reductase gene (gene, FDXR; protein, FR) increase drastically after 5-FU treatment in various cell lines including colorectal cancer. The induction is mediated by p53 and enhanced reactive oxygen species (ROS)-associated apoptosis. Thus, knowledge about FDXR expression in human tissue and expression of the known splice variants is critical for understanding this finding. A sensitive and specific reverse transcriptase polymerase chain reaction (RT-PCR) assay for quantification of FDXR mRNA levels including the splice variants, a biological active variant (−18 bp) and an inactive variant (+18 bp), was developed and used to measure mRNAs after 5-FU chemotherapy in colorectal tissues of 40 cancer patients prior to and after treatment with 5-FU for 14 days. Before treatment, the great majority of normal tissues expressed the splice variants in a 100:1 ratio in favor of the (−18-variant similar to what has been reported for other tissues. In tumors, the mRNA levels of total FDXR and splice variants were approximately 2-fold higher compared to the normal tissue. After 5-FU treatment, levels of the +18-variant increased 17-fold in tumors and 31-fold in normal tissues, clearly shifting the ratio towards the +18-form. 5-FU-mediated (−18-variant induction (>1) in normal (12/17) and tumor tissues (12/16) was apparently associated with response, while a balanced ratio (0.1-2) was associated with 5-FU resistance (n=5) based on the histological evaluation of the tissues.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Influence of 5-fluorouracil on ferredoxin reductase mRNA splice variants in colorectal carcinomas

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