Cited by 342Cancer-related Molecular PathwaysTelomeres, Telomerase, and SenescenceMicrotubule and mitosis dynamics

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The Requirement for Cyclin D Function in Tumor Maintenance

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Choi, Yoon Jong, Li, Xiaoyu, Hydbring, Per, Sanda, Takaomi, Stefano, Joanna, Christie, Amanda L., Signoretti, Sabina, Look, A. Thomas, Kung, Andrew L., von Boehmer, Harald, Sicinski, Piotr·2012·Cancer Cell

DOI 10.1016/j.ccr.2012.09.015PMC PMC3487466

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Abstract

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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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: Choi, Yoon Jong
Li, Xiaoyu
Hydbring, Per
Sanda, Takaomi
Signoretti, Sabina
Look, A. Thomas
Kung, Andrew L.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2012-10
Volume: 22
Issue: 4
Pages: 438-451
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2012.09.015
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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The Requirement for Cyclin D Function in Tumor Maintenance

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