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

Sarah J. Freemantle, Ethan Dmitrovsky

Research output: Contribution to journalShort survey

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.

Original languageEnglish (US)
Pages (from-to)1513-1518
Number of pages6
JournalCancer Prevention Research
Volume3
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

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Cyclin E
Transgenic Mice
Lung Neoplasms
Lung
Carcinogenesis
Non-Small Cell Lung Carcinoma
Hyperplasia
Adenocarcinoma
Therapeutics
Cyclin-Dependent Kinase 2
Alveolar Epithelial Cells
Cell Line
Chromosomal Instability
Hedgehogs
Proteasome Endopeptidase Complex
MicroRNAs
Carcinogens
Antineoplastic Agents
Neoplasms
Cell Cycle

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cyclin E transgenic mice : Discovery tools for lung cancer biology, therapy, and prevention. / Freemantle, Sarah J.; Dmitrovsky, Ethan.

In: Cancer Prevention Research, Vol. 3, No. 12, 01.12.2010, p. 1513-1518.

Research output: Contribution to journalShort survey

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