RRC ID 15512
Author Schartl M, Wilde B, Laisney JA, Taniguchi Y, Takeda S, Meierjohann S.
Title A mutated EGFR is sufficient to induce malignant melanoma with genetic background-dependent histopathologies.
Journal J Invest Dermatol
Abstract Melanoma is a tumor with a very low cure rate once metastasized. Although many genes important for melanoma induction, transformation, and metastasis have been identified, the process of melanomagenesis is only partly understood. Melanoma mediators are easiest to investigate in cell culture models, but animal models are required to evaluate their importance in the context of the whole organism. Here, we describe a transgenic melanoma model in medaka. The oncogenic receptor tyrosine kinase, Xmrk, responsible for melanoma formation in Xiphophorus, was stably expressed under the control of a pigment cell-specific promoter. The transgenic fish developed pigment cell tumors with a penetrance of 100%. The model was used for monitoring the in vivo relevance of several apoptosis and differentiation genes, and for induction of melanoma-relevant signal transduction pathways. We found that Stat5 activation, and Mitf and Bcl-2 levels correlated with a more aggressive stage of the malignancy. Interestingly, different types of pigment cell tumors occurred depending on the genetic background, namely invasive melanoma, uveal melanoma, or exophytic and less aggressive pigment cell tumors called xanthoerythrophoroma. Furthermore, on p53 mutant background, the expression of xmrk led to the appearance of giant focal pigment cell tumors, whereas tumor onset was unchanged compared with wild-type medaka.
Volume 130(1)
Pages 249-58
Published 2010-1-1
DOI 10.1038/jid.2009.213
PII S0022-202X(15)34518-8
PMID 19609310
MeSH Animals Animals, Genetically Modified Cyprinodontiformes / genetics* Disease Models, Animal Female Fish Diseases / genetics Fish Proteins / genetics* Fish Proteins / metabolism Inhibitor of Apoptosis Proteins / genetics Male Melanoma / genetics* Melanoma / metabolism Melanoma / secondary Microphthalmia-Associated Transcription Factor / genetics Oryzias / genetics* Proto-Oncogene Proteins c-bcl-2 / genetics Receptor Protein-Tyrosine Kinases / genetics* Receptor Protein-Tyrosine Kinases / metabolism SOXE Transcription Factors / genetics Signal Transduction / physiology Skin Neoplasms / genetics* Skin Neoplasms / metabolism Skin Neoplasms / pathology
IF 7.143
Times Cited 53
Medaka database HB32C i-3 CabR' p53(E241x) (MT894)