ArticleProceedings of the National Academy of Sciences of the United States of America2002
Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 144 citations in OpenAlex.
- Preclinical Models of Neuroendocrine Neoplasia.Cancers · 2022Review
- Melanoma models for the next generation of therapies.Cancer cell · 2021Review
- Pheochromocytoma/paraganglioma preclinical models: which to use and why?Endocrine connections · 2020Review
- Review
- PTEN in Hereditary and Sporadic Cancer.Cold Spring Harbor perspectives in medicine · 2020Review
- Rodent models of pheochromocytoma, parallels in rodent and human tumorigenesis.Cell and tissue research · 2018Review
- PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma.PLoS genetics · 2016Article
- Loss of JUNB/AP-1 promotes invasive prostate cancer.Cell death and differentiation · 2015Article
- Current State of Animal (Mouse) Modeling in Melanoma Research.Cancer growth and metastasis · 2015Review
- Single and Multiple Gene Manipulations in Mouse Models of Human Cancer.Cancer growth and metastasis · 2015Review
- Akt-dependent activation of mTORC1 complex involves phosphorylation of mTOR (mammalian target of rapamycin) by IκB kinase α (IKKα).The Journal of biological chemistry · 2014Article
- PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a.Aging cell · 2013Article
- Genetically engineered mouse models of prostate cancer.Molecular oncology · 2013Review
- Acquired hypermethylation of the P16INK4A promoter in abdominal paraganglioma: relation to adverse tumor phenotype and predisposing mutation.Endocrine-related cancer · 2013Article
- Driver mutations in melanoma: lessons learned from bench-to-bedside studies.Current oncology reports · 2012Review
- Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer.The Journal of clinical investigation · 2012Article
- Genetic alterations of PTEN in human melanoma.Cellular and molecular life sciences : CMLS · 2012Review
- Murine models and cell lines for the investigation of pheochromocytoma: applications for future therapies?Endocrine pathology · 2012Review
- Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway.Advances in urology · 2012Article
- PTEN loss in the continuum of common cancers, rare syndromes and mouse models.Nature reviews. Cancer · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Dual inactivation of PTEN and INK4a/ARF tumor suppressor genes is a common feature observed in a broad spectrum of human cancer types. To validate functional collaboration between these genes in tumor suppression, we examined the biological consequences of Pten and/or Ink4a/Arf deficiency in cells and mice. Relative to single mutant controls, Ink4a/Arf-/-Pten+/- mouse embryonic fibroblast cultures exhibited faster rates of growth in reduced serum, grew to higher saturation densities, produced more colonies upon low density seeding, and showed increased susceptibility to transformation by oncogenic H-Ras. Ink4a/Arf deficiency reduced tumor-free survival and shortened the latency of neoplasias associated with Pten heterozygosity, specifically pheochromocytoma, prostatic intraepithelial neoplasia, and endometrial hyperplasia. Compound mutant mice also exhibited an expanded spectrum of tumor types including melanoma and squamous cell carcinoma. Functional synergy between Ink4a/Arf and Pten manifested most prominently in the development of pheochromocytoma, prompting an analysis of genes and loci implicated in this rare human neoplasm. The classical pheochromocytoma genes Ret, Vhl, and Nf-1 remained intact, a finding consistent with the intersection of these genes with pathways engaged by Pten and Ink4a/Arf. Notably, conventional and array-comparative genomic hybridization revealed frequent loss of distal mouse chromosome 4 in a region syntenic to human chromosome 1p that is implicated in human pheochromocytoma. This study provides genetic evidence of collaboration between Pten and Ink4a/Arf in constraining the growth and oncogenic transformation of cultured cells and in suppressing a wide spectrum of tumors in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.