The tumor-suppressive functions of the human INK4A locus
Open accessAbstract
The INK4A locus is often inactivated in human cancer. INK4A encodes for p14ARF and p16INK4A that inhibit growth through p53 and pRb, respectively. We used RNA interference vectors in transformation assays of human primary cells to analyze tumor-suppressive functions. We first show that a concerted inactivation of pRb and p53 is required for transformation. We then demonstrate that loss of p14ARF enhances growth in a p53-dependent manner but has little tumorigenic effect. In contrast, suppression of p16INK4A expression does not affect cellular proliferation but synergizes with p53 loss to accelerate growth and cause transformation. Our results delineate the functions of the human INK4A genes in normal and tumorigenic growth.
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The shRNA against p53 was previously validated to specifically inactivate p53.
“To study the role of p53, we used a small hairpin RNA (shRNA) previously validated to specifically inactivate p53 (47).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [47]
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- Authors
- Voorhoeve, P. M., & Agami, R.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Corresponding author
- Agami, Reuven
- ORCID
- Agami, Reuven
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 4
- Issue
- 4
- Pages
- 311-319
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1972134119
- Cited by
- 194
- References
- 11
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 6 · 2022: 1 · 2021: 8 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 12 · 2012: 11
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- p16INK4a, p14ARF, p53, retinoblastoma protein, tumor suppression, cell transformation, RNA interference, cell proliferation, tumor growth
- MeSH terms
- Cell Division, Cells, Cultured, Fibroblasts, HeLa Cells, Humans, Mutation, Genes, ras, Skin, Tumor Suppressor Protein p53, Retinoblastoma Protein, Gene Deletion, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Protein p14ARF, RNA, Small Interfering
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