In:
Pigment Cell & Melanoma Research, Wiley, Vol. 32, No. 2 ( 2019-03), p. 248-258
Abstract:
In humans, the CDKN 2A locus encodes two transcripts, INK 4A 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 CDKN 2A , 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.
Type of Medium:
Online Resource
ISSN:
1755-1471
,
1755-148X
DOI:
10.1111/pcmr.2019.32.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2425880-5
Permalink