ArticleProceedings of the National Academy of Sciences of the United States of America1996
Ribonucleotide reductase R2 component is a novel malignancy determinant that cooperates with activated oncogenes to determine transformation and malignant potential.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 103 citations in OpenAlex.
- DNA damage repair-related methylated genes RRM2 and GAPDH are prognostic biomarkers associated with immunotherapy for lung adenocarcinoma.Genetics and molecular biology · 2025Article
- Prognostic and Immunological Potential of Ribonucleotide Reductase Subunits in Liver Cancer.Oxidative medicine and cellular longevity · 2023Article
- Article
- miR-211 regulates the expression ofOncology letters · 2018Article
- Knockdown ofOncology letters · 2018Article
- p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis.Cell cycle (Georgetown, Tex.) · 2017Article
- Clinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy?Journal of cancer research and clinical oncology · 2017Review
- Targeting Nucleotide Biosynthesis: A Strategy for Improving the Oncolytic Potential of DNA Viruses.Frontiers in oncology · 2017Review
- T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell proliferation and induce cell apoptosis in leukemia cell lines.Journal of experimental & clinical cancer research : CR · 2015Article
- Review
- Phase I study of GTI-2040, a ribonucleotide reductase antisense, with high dose cytarabine in patients with relapsed/refractory acute myeloid leukemia.Leukemia & lymphoma · 2014Article
- RRM2 regulates Bcl-2 in head and neck and lung cancers: a potential target for cancer therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers.Clinical science (London, England : 1979) · 2013Article
- Article
- [Ribonucleotide reductase and non-small cell lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2012Review
- Emerging roles of the ribonucleotide reductase M2 in colorectal cancer and ultraviolet-induced DNA damage repair.World journal of gastroenterology · 2012Article
- Current progress of siRNA/shRNA therapeutics in clinical trials.Biotechnology journal · 2011Review
- Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer.Cancer research · 2011Article
- Novel strategy with gemcitabine for advanced pancreatic cancer.ISRN oncology · 2011Article
- Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in mice.Nucleic acids research · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribonucleotide reductase is a highly regulated cell cycle-controlled activity that is essential for DNA synthesis and repair. A retroviral vector for the R2 component of mammalian ribonucleotide reductase, the rate-limiting protein for enzyme activity and DNA synthesis in proliferating cells, was constructed and introduced into mammalian cells. Expression of Myc epitope-tagged R2 protein in benign BALB/c 3T3 and NIH 3T3 cells leads to a greatly increased frequency of focus formation in cooperation with H-ras transformation. Four lines of H-ras-transformed mouse 10T1/2 fibroblasts showed increased growth efficiency in soft agar after infection with the recombinant R2 expression virus vector. Furthermore, cells with altered R2 expression also exhibited significantly reduced subcutaneous tumor latency and increased tumor growth rates in syngeneic mice, and showed markedly elevated metastatic potential in lung metastasis assays. The results indicate that altered R2 gene expression cooperates with ras in mechanisms of malignant progression. A major Ras pathway involves the Raf-1 protein, which is recruited to the plasma membrane for activation. We show that recombinant R2 expression leads to significant increases in membrane-associated Raf-1 protein and mitogenactivating protein kinase-2 activity suggesting a mechanism for the observed Ras/R2 synergism. In support of this finding, we observed that activated Rac-1, which operates parallel to Raf-1 and cooperates with Raf-1 in Ras activated pathways, also cooperates with R2 in cellular transformation. These studies demonstrate that the R2 protein can participate in other critical cellular functions in addition to ribonucleotide reduction, and that deregulated R2 is a novel tumor progressor determinant that cooperates in oncogene-mediated mechanisms, which control malignant potential.
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Registered trials
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