Transcriptional control analyses of the Xiphophorus melanoma oncogene

Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP
Janine RegneriManfred Schartl

Abstract

Melanoma development in interspecific hybrids of Xiphophorus is induced by the overexpression of the mutationally activated receptor tyrosine kinase Xmrk in pigment cells. Based on the melanocyte specificity of the transcriptional upregulation, a pigment cell-specific promoter region was postulated for xmrk, the activity of which is controlled in healthy purebred fish by the molecularly still unidentified regulator locus R. However, as yet the xmrk promoter region is still poorly characterized. In order to contribute to a better understanding of xmrk expression regulation, we performed a functional analysis of the entire putative gene regulatory region of the oncogene using conventional plasmid-based reporter systems as well as a newly established method employing BAC-derived luciferase reporter constructs in melanoma and non-melanoma cell lines. Using the melanocyte-specific mitfa promoter as control, we could demonstrate that our in vitro system is able to reliably monitor regulation of transcription through cell type-specific regulatory sequences. We found that sequences within 200kb flanking the xmrk oncogene do not lead to any specific transcriptional activation in melanoma compared to control cells. Hence, xmrk reporter c...Continue Reading

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Citations

Oct 27, 2015·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Lynne A Fieber
Aug 16, 2016·Marine Environmental Research·Adélaïde LereboursJeanette M Rotchell
Aug 18, 2018·Pigment Cell & Melanoma Research·Janine RegneriManfred Schartl
Feb 5, 2021·Frontiers in Cell and Developmental Biology·Mateus C AdolfiManfred Schartl

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