NDLI: Increased expression of the large subunit of ribonucleotide reductase is involved in resistance to gemcitabine in human mammary adenocarcinoma cells.

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Increased expression of the large subunit of ribonucleotide reductase is involved in resistance to gemcitabine in human mammary adenocarcinoma cells.

Content Provider	Semantic Scholar
Author	Jordheim, Lars Petter Guittet, Olivier Lepoivre, Michel Galmarini, Carlos M. Dumontet, Charles
Copyright Year	2005
Abstract	Resistance to cytotoxic nucleoside analogues is a major problem in cancer treatment. The cellular mechanisms involved in this phenomenon have been studied for several years, and some factors have been identified. However, this resistance seems to be multifactorial and more studies are needed to gain better insight into this domain. For this purpose, we developed a gemcitabine-resistant cell line (MCF7 1K) from the human mammary adenocarcinoma MCF7 strain by prolonged exposure to gemcitabine in vitro. MCF7 1K cells are highly resistant to gemcitabine (533-fold) and cross-resistance is observed with araC (47-fold), triapine (14-fold), and hydroxyurea (6.7-fold). Quantitative real-time reverse transcription-PCR and Western blot analysis showed an increase in the gene and protein expression of the large subunit of ribonucleotide reductase, R1. Ribonucleotide reductase activity was also significantly increased in the gemcitabine-resistant cells. Study of genomic DNA showed 12-fold increase in R1 gene dosage in MCF7 1K cells. In contrast, the gene and protein expression of the small subunit of ribonucleotide reductase, R2, were not modified in this cell line. These results show that gemcitabine resistance can be associated with genetic modifications of target genes in malignant cells, and suggest that the large subunit of human ribonucleotide reductase is involved in the cellular response to gemcitabine.
Starting Page	139
Ending Page	140
Page Count	2
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://mct.aacrjournals.org/content/molcanther/4/8/1268.full.pdf
PubMed reference number	16093443v1
Volume Number	4
Issue Number	8
Journal	Molecular cancer therapeutics
Language	English
Access Restriction	Open
Subject Keyword	MCF-7 Cells Mammary adenocarcinoma Nucleosides Reverse Transcription Ribonucleotide Reductase Ribonucleotides Triapine Western Blot cancer cell gemcitabine hydroxyurea protein expression
Content Type	Text
Resource Type	Article

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