Evidence map›Paper›PMID 21170325›Full record

ArticlePloS one2010

Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.

Cristina Santoriello, Elisa Gennaro, Viviana Anelli, Martin Distel, Amanda Kelly, Reinhard W Köster, Adam Hurlstone, Marina Mione

Abstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

76 citing papers in PubMed.

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  20. Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity.Frontiers in cell and developmental biology · 2021
    Review

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Cristina SantorielloIFOM Foundation-FIRC Institute of Molecular Oncology, Milan, Italy.
Elisa Gennaro
Viviana Anelli
Martin Distel
Amanda Kelly
Reinhard W Köster
Adam Hurlstone
Marina Mione

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK C11876/A4495
6 · The paper itself

Abstract

backgroundMelanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed. METHODOLOGY AND PRINCIPAL

findingsUsing the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period. CONCLUSIONS AND SIGNIFICANCE: This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsAnimals, Genetically ModifiedDisease Models, AnimalDisease ProgressionGenes, p53MelanocytesMelanomaModels, GeneticPhenotypePromoter Regions, GeneticProto-Oncogene Proteins c-kitProto-Oncogene Proteins p21(ras)PTEN PhosphohydrolaseSkin NeoplasmsTransgenesProto-Oncogene Proteins c-kitProto-Oncogene Proteins p21(ras)PTEN Phosphohydrolase

Identifiers

PMID21170325
PMCPMC3000817

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Registered trials

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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.