Analysis of the Putative Tumor Suppressor Gene cdkn2ab in Pigment Cells and Melanoma of Xiphophorus and Medaka

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dc.contributor.authorRegneri, Janine
dc.contributor.authorKlotz, Barbara
dc.contributor.authorWilde, Brigitta
dc.contributor.authorKottler, Verena A.
dc.contributor.authorHausmann, Michael
dc.contributor.authorKneitz, Susanne
dc.contributor.authorRegensburger, Martina
dc.contributor.authorMaurus, Katja
dc.contributor.authorGotz, Ralph
dc.contributor.authorLu, Yuan
dc.contributor.authorWalter, Ronald B.
dc.contributor.authorHerpin, Amaury
dc.contributor.authorSchartl, Manfred
dc.date.accessioned2020-03-16T19:38:00Z
dc.date.available2020-03-16T19:38:00Z
dc.date.issued2019-03
dc.description.abstractIn 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.
dc.description.departmentChemistry and Biochemistry
dc.description.versionThis is the accepted manuscript version of an article published in Pigment Cell and Melanoma Research.
dc.formatText
dc.format.extent21 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationRegneri, J., Klotz, B., Wilde, B., Kottler, V. A., Hausmann, M., Kneitz, S., Regensburger, M., Maurus, K., Gotz, R., Lu, Y., Walter, R. B., Herpin, A., & Schartl, M. (2019). Analysis of the putative tumor suppressor gene cdkn2ab in pigment cells and melanoma of Xiphophorus and medaka. Pigment Cell and Melanoma Research, 32(2), pp. 248–258.
dc.identifier.doihttps://doi.org/10.1111/pcmr.12729
dc.identifier.issn1755-1471
dc.identifier.urihttps://hdl.handle.net/10877/9454
dc.language.isoen
dc.publisherWiley
dc.sourcePigment Cell and Melanoma Research, 2019, Vol. 32, No. 2, pp. 248–258.
dc.subjectcell cycle regulation
dc.subjectnevi
dc.subjectp16/INK4A
dc.subjectsenescence
dc.subjectxmrk
dc.subjectChemistry and Biochemistry
dc.titleAnalysis of the Putative Tumor Suppressor Gene cdkn2ab in Pigment Cells and Melanoma of Xiphophorus and Medaka
dc.typeArticle

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