Analysis of the putative tumor suppressor genecdkn2abin pigment cells and melanoma ofXiphophorusand medaka

Autor: Susanne Kneitz, Verena A. Kottler, Janine Regneri, Barbara Klotz, Katja Maurus, Michael Hausmann, Yuan Lu, Ronald B. Walter, Amaury Herpin, Brigitta Wilde, Manfred Schartl, Martina Regensburger, Ralph Götz
Přispěvatelé: Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, Department of Chemistry & Biochemistry - Molecular Biosciences Research Group, Texas State University, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Germany and Hagler Institute for Advanced Study and Department of Biology, Texas A&M University System, This work was supported by the National Institutes of Health under award number R24OD018555, subaward number 215420C
Rok vydání: 2018
Předmět:
mélanome
0301 basic medicine
senescence
Carcinogenesis
[SDV]Life Sciences [q-bio]
Melanoma
Experimental
Oryzias
markings
Cyprinodontiformes
Gene Knockout Techniques
0302 clinical medicine
poisson
CDKN2A
pigmentation
Genes
Tumor Suppressor
poeciliidae
Phylogeny
Melanoma
Xiphophorus
Phenotype
homme
Gene Expression Regulation
Neoplastic
Oncology
Multigene Family
030220 oncology & carcinogenesis
nevi
Melanocytes
cell cycle regulation
régulation cellulaire
expression des gènes
tumor
Tumor suppressor gene
Transgene
Dermatology
Biology
Article
General Biochemistry
Genetics and Molecular Biology
Evolution
Molecular
03 medical and health sciences
tumeur
man
medicine
cancer
Animals
human
adrianichthyidae
Epigenetics
p16/INK4A
neoplasms
Gene
Cyclin-Dependent Kinase Inhibitor p16
fish
medaka
medicine.disease
biology.organism_classification
Xiphphorus
030104 developmental biology
Cancer research
humain
xmrk
Zdroj: Pigment Cell and Melanoma Research
Pigment Cell and Melanoma Research, 2019, 32 (2), pp.248-258. ⟨10.1111/pcmr.12729⟩
ISSN: 1755-148X
1755-1471
DOI: 10.1111/pcmr.12729
Popis: In humans, the CDKN2A locus encodes two transcripts, INK4A and ARF. Inactivation of either one by mutations or epigenetic changes is a frequent signature of malignant melanoma and one of the most relevant entry points for melanomagenesis. To analyze whether cdkn2ab, the fish ortholog of CDKN2A, has a similar function as its human counterpart, we studied its action in fish models for human melanoma. Overexpression of cdkn2ab in a Xiphophorus melanoma cell line led to decreased proliferation and induction of a senescence‐like phenotype, indicating a melanoma‐suppressive function analogous to mammals. Coexpression of Xiphophorus cdkn2ab in medaka transgenic for the mitfa:xmrk melanoma‐inducing gene resulted in full suppression of melanoma development, whereas CRISPR/Cas9 knockout of cdkn2ab resulted in strongly enhanced tumor growth. In summary, this provides the first functional evidence that cdkn2ab acts as a potent tumor suppressor gene in fish melanoma models.
Databáze: OpenAIRE
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