Cyclin E transgenic mice: discovery tools for lung cancer biology, therapy, and prevention.

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  • Author(s): Freemantle SJ;Freemantle SJ; Dmitrovsky E
  • Source:
    Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2010 Dec; Vol. 3 (12), pp. 1513-8.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101479409 Publication Model: Print Cited Medium: Internet ISSN: 1940-6215 (Electronic) Linking ISSN: 19406215 NLM ISO Abbreviation: Cancer Prev Res (Phila) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Philadelphia, PA : American Association for Cancer Research
    • Subject Terms:
      Disease Models, Animal*; Adenocarcinoma/*prevention & control ; Antineoplastic Agents/*therapeutic use ; Cyclin E/*genetics ; Lung Neoplasms/*prevention & control; Adenocarcinoma/genetics ; Animals ; Cyclin E/antagonists & inhibitors ; Humans ; Lung Neoplasms/genetics ; Mice ; Mice, Transgenic
    • Abstract:
      Lung cancer is the leading cause of cancer-related mortality in the United States and many other countries. This fact underscores the need for clinically relevant models to increase our understanding of lung cancer biology and to help design and implement preventive and more effective therapeutic interventions for lung cancer. New murine transgenic models of non-small cell lung cancer (NSCLC) have been engineered for this purpose. In one such model, overexpression of the cell-cycle regulator cyclin E is targeted to type II alveolar lung cells; dysplasia, hyperplasia, and adenocarcinoma forming in this model have features recapitulating key features of carcinogenesis found in NSCLC patients. These features include the presence of chromosomal instability, pulmonary dysplasia, and hyperplasia, hedgehog-pathway activation, single and multiple adenocarcinomas, and even metastases. Cell lines that expressed either a human wild-type or mutant (proteasome-degradation-resistant) form of cyclin E were derived from the transgenic mouse lung cancers. These cell lines are transplantable into syngeneic host mice, which rapidly develop lung tumors and thus facilitate the rapid testing of agents targeting lung carcinogenesis. These transgenic and transplantable models have already aided in the discovery of oncogenic and growth-suppressive microRNAs and in the identification of a novel antineoplastic mechanism of action for inhibitors of cyclin-dependent kinase 2. This review discusses the general utility of murine carcinogen-induced and transgenic models of lung carcinogenesis and describes the optimization of cyclin E-overexpressing lung carcinogenesis models and their use in testing candidate agents for the prevention and therapy of lung cancer.
      (©2010 AACR.)
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    • Grant Information:
      R03-CA132166 United States CA NCI NIH HHS; R01 CA087546-04 United States CA NCI NIH HHS; R03 CA130102-02 United States CA NCI NIH HHS; P30 CA023108 United States CA NCI NIH HHS; R01 CA087546-08 United States CA NCI NIH HHS; R01 CA087546 United States CA NCI NIH HHS; R01 CA087546-03 United States CA NCI NIH HHS; R01 CA111422-04 United States CA NCI NIH HHS; R01 CA087546-10 United States CA NCI NIH HHS; R03 CA132166 United States CA NCI NIH HHS; R03 CA130102-01 United States CA NCI NIH HHS; R01 CA111422-06 United States CA NCI NIH HHS; R01-CA087546 United States CA NCI NIH HHS; R01 CA111422-05A1 United States CA NCI NIH HHS; R01 CA111422 United States CA NCI NIH HHS; R01 CA087546-09 United States CA NCI NIH HHS; R01 CA087546-06A1 United States CA NCI NIH HHS; R03 CA132166-01 United States CA NCI NIH HHS; R01 CA111422-02 United States CA NCI NIH HHS; R03 CA132166-02 United States CA NCI NIH HHS; R01 CA111422-01A1 United States CA NCI NIH HHS; R01 CA087546-05 United States CA NCI NIH HHS; R03 CA130102 United States CA NCI NIH HHS; R01-CA111422 United States CA NCI NIH HHS; R03-CA130102 United States CA NCI NIH HHS; R01 CA087546-01 United States CA NCI NIH HHS; R01 CA111422-03 United States CA NCI NIH HHS; R01 CA087546-02 United States CA NCI NIH HHS; R01 CA087546-07 United States CA NCI NIH HHS
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Cyclin E)
    • Publication Date:
      Date Created: 20101215 Date Completed: 20110405 Latest Revision: 20211020
    • Publication Date:
      20221213
    • Accession Number:
      PMC3058281
    • Accession Number:
      10.1158/1940-6207.CAPR-10-0297
    • Accession Number:
      21149327