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The Requirement for Cyclin D Function in Tumor Maintenance
Open accessAbstract
D-cyclins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains that allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D-associated kinase activity in mice bearing ErbB2-driven mammary carcinomas triggered tumor cell senescence, without compromising the animals' health. Ablation of cyclin D3 in mice bearing Notch1-driven T cell acute lymphoblastic leukemias (T-ALL) triggered tumor cell apoptosis. Such selective killing of leukemic cells can also be achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Inhibition of cyclin D-kinase activity represents a highly-selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues.
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“Depending on the cell type and the transforming event, some Rb-positive cells undergo quiescence and others undergo senescence when treated with CDK4/6 inhibitors (Baughn et al., 2006; Choi et al., 2012; Kovatcheva et al., 2015; Michaud et al., 2010; Puyol et al., 2010).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Choi et al., 2012
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“In T-cell acute lymphoblastic leukemia (T-ALL), inhibition of CDK6 or genetic repression of cyclin D3 induces apoptosis (Choi et al., 2012; Sawai et al., 2012).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Choi et al., 2012
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Metadata
- Authors
- Choi, Y. J., Li, X., Hydbring, P., Sanda, T., Stefano, J., Christie, A. L., Signoretti, S., Look, A. T., Kung, A. L., von Boehmer, H., & Sicinski, P.
- Affiliations
- Harvard University (US)
- Boston Children's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 22
- Issue
- 4
- Pages
- 438-451
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3487466
- OpenAlex
- W2126821691
- Cited by
- 342
- References
- 56
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 23 · 2023: 27 · 2022: 30 · 2021: 20 · 2020: 31 · 2019: 29 · 2018: 32 · 2017: 36 · 2016: 24 · 2015: 19 · 2014: 27 · 2013: 17 · 2012: 3
- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 380 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01 CA080111, P01 CA109901, R01 CA083688)
- National Cancer Institute (1K99CA157951)
- Novartis
- Children’s Leukemia Research Association
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- cyclin D1, cyclin D3, tumor maintenance, cell cycle, tumor cell senescence, apoptosis, breast cancer, targeted cancer therapy
- MeSH terms
- Animals, Female, Humans, Mammary Neoplasms, Experimental, Neoplasms, Apoptosis, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Cyclin-Dependent Kinase 4, Mice, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Cyclin D, Cell Cycle Checkpoints
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