E2F3 Loss Has Opposing Effects on Different pRB-Deficient Tumors, Resulting in Suppression of Pituitary Tumors but Metastasis of Medullary Thyroid Carcinomas
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The E2F transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor. We have previously shown that E2F3 plays a critical role in mediating the mitogen-induced activation of E2F-responsive genes and contributes to both the inappropriate proliferation and the p53-dependent apoptosis that arise in pRB-deficient embryos. Here we show that E2F3 also has a significant effect on the phenotype of tumor-prone Rb(+/-) mice. The absence of E2F3 results in a significant expansion in the life spans of these animals that correlates with a dramatic alteration in the tumor spectrum. E2F3 loss suppresses the development of the pituitary tumors that normally account for the death of Rb(+/-) mice. However, it also promotes the development of medullary thyroid carcinomas yielding metastases at a high frequency. This increased aggressiveness does not seem to result from any change in p53 levels or activity in these tumors. We show that, instead, E2F3 loss leads to an increase in the rate of tumor initiation. Finally, analysis of Rb(+/-); E2f3(+/-) mice shows that this tumor-suppressive function of E2F3 is dose dependent.
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E2F3 inactivation enhances metastatic potential of RB-deficient thyroid carcinomas in vivo.
“However, E2F3 inactivation has also been found to enhance the metastatic potential of RB-deficient thyroid carcinomas in vivo142.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [142]
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- Authors
- Ziebold, U., Lee, E. Y., Bronson, R. T., & Lees, J. A.
- Affiliations
- Massachusetts Institute of Technology (US)
- Tufts University (US)
- Corresponding author
- Lees, Jacqueline A.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-09-01
- Volume
- 23
- Issue
- 18
- Pages
- 6542-6552
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC193688
- OpenAlex
- W2125096346
- Cited by
- 94
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 8 · 2013: 4 · 2012: 3
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Cancer Institute (P01CA042063)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- E2F3, retinoblastoma protein, pituitary tumors, medullary thyroid carcinoma, metastasis, tumor initiation, tumor spectrum, Rb, E2F transcription factors, tumor suppressor function
- MeSH terms
- Animals, Animals, Newborn, Female, Fetal Viability, Heterozygote, Longevity, Male, Mice, Mutant Strains, Mutation, Neoplasm Metastasis, Phenotype, Pituitary Neoplasms, Thyroid Neoplasms, Transcription Factors, Tumor Suppressor Protein p53, Retinoblastoma Protein, Carcinoma, Medullary, Gene Dosage, E2F3 Transcription Factor, Mice
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