Transcriptome sequencing of melanocytic nevi and melanomas from <i><scp>G</scp>rm1</i> transgenic mice to determine melanoma driver mutations

Jel, Miriam M. de; Engelmann, Julia C.; Kunz, Manfred; Schiffner, Susanne; Kuphal, Silke; Bosserhoff, Anja‐Katrin

doi:10.1111/pcmr.12244

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…Only 13 of 1,009 analyzed malignant melanoma samples in total harbor a SELENBP 1 mutation (data not shown). The result was supported by the finding that RNA-sequencing analysis of the Tg( Grm1 ) mouse model uncovered also no melanoma-associated mutations or single nucleotide variations [ 6 ].…”

Section: Resultsmentioning

confidence: 88%

“…Interestingly, GRM1 up-regulation is also present in human melanoma cell lines and tissues [ 2 , 4 , 5 ]. Since transcriptome sequencing did not reveal melanoma-associated mutations or single nucleotide variations in Tg( Grm1 ) mice [ 6 ], we assume, besides Grm1 overexpression, epigenetic events or changes in gene expression are important for driving melanoma development and progression in this mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Selenium-binding protein 1 is down-regulated in malignant melanoma

Schott¹,

Jel²,

Engelmann

et al. 2018

Oncotarget

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Selenium-binding protein 1 (SELENBP1) expression is reduced in various epithelial cancer entities compared to corresponding normal tissue and has already been described as a tumor suppressor involved in the regulation of cell proliferation, senescence, migration and apoptosis. We identified SELENBP1 to be down-regulated in cutaneous melanoma, a malignant cancer of pigment-producing melanocytes in the skin, which leads to the assumption that SELENBP1 also functions as tumor suppressor in the skin, as shown by others e.g. for prostate or lung carcinoma.However, in vitro analyses indicate that SELENBP1 re-expression in human melanoma cell lines has no impact on cell proliferation, migration or tube formation of the tumor cells themselves when compared to control-transfected cells. Interestingly, supernatant taken from melanoma cell lines transfected with a SELENBP1 re-expression plasmid led to suppression of vessel formation of HMEC cells. Furthermore, SELENBP1 re-expression alters the sensitivity of melanoma cells for Vemurafenib treatment.The data also hint to a functional interaction of SELENBP1 with GPX1 (Glutathione peroxidase 1). Low SELENBP1 mRNA levels correlate inversely with GPX1 expression in melanoma. The re-expression of SELENBP1 combined with down-regulation of GPX1 expression led to reduction of the proliferation of melanoma cells. In summary, SELENBP1 influences the tumor microenvironment and SELENBP1 action is functionally influenced by GPX1.

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Section: Resultsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Selenium-binding protein 1 is down-regulated in malignant melanoma

Schott¹,

Jel²,

Engelmann

et al. 2018

Oncotarget

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“…In order to define CYLD-dependent deregulated genes and the underlying mechanism resulting in increased tumor growth in the Cyld -knockout mice, RNA sequencing was performed 21 . Here, primary tumor tissue from Tg( Grm1 ) Cyld +/+ versus Tg( Grm1 ) Cyld −/− was used to determine the gene expression profile ( p -value < 0.05; 0.66 < FC > 1.5; FC = foldchange).…”

Section: Resultsmentioning

confidence: 99%

“…Sample processing was performed at an Affymetrix Service Provider and Core Facility, “KFB - Center of Excellence for Fluorescent Bioanalytics” (Regensburg, Germany; www.kfb-regensburg.de) 21 . For the identification of known and predicted protein–protein interactions, STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database was used 47 .…”

Section: Methodsmentioning

confidence: 99%

Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model

et al. 2019

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The deubiquitinase cylindromatosis (CYLD) is a well-known tumor suppressor, found to be down regulated in many cancer types including breast cancer, colon carcinoma and malignant melanoma. CYLD is suppressed in human melanoma cells by the transcriptional repressor SNAIL1 leading to an increase of their proliferative, invasive and migratory potential. To gain additional insights into the distinct function of this tumor suppressor gene a new mouse model Tg(Grm1)Cyld−/− was generated. Herewith, we demonstrate that Cyld-deficiency leads to earlier melanoma onset and accelerated tumor growth and metastasis in the GRM1 melanoma mouse model. First, RNA sequencing data revealed a potential role of CYLD in the regulation of genes involved in proliferation, migration and angiogenesis. Experiments using cell lines generated from both primary and metastatic melanoma tissue of Tg(Grm1) Cyld−/− and Tg(Grm1) Cyld+/+ mice confirmed that loss of CYLD enhances the proliferative and migratory potential, as well as the clonogenicity in vitro. Moreover, we could show that Cyld-knockout leads to increased vasculogenic mimicry and enhanced (lymph-) angiogenesis shown by tube formation assays, immunohistochemistry and mRNA expression analyses. In summary, our findings reveal new functional aspects of CYLD in the process of (lymph-) angiogenesis and demonstrate its importance in the early process of melanoma progression.

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The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations

Meeth

Wang

Micevic

et al. 2016

Pigment Cell Melanoma Res

248

250

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Summary The remarkable success of immune therapies emphasizes the need for immune competent cancer models. Elegant genetically engineered mouse models of a variety of cancers have been established, but their effective use is limited by cost and difficulties in rapidly generating experimental data. Some mouse cancer cell lines are transplantable to immunocompetent host mice and have been utilized extensively to study cancer immunology. Here we describe a comprehensive system of mouse melanoma cell lines that are syngeneic to C57Bl/6J, have well-defined human-relevant driver mutations, and are genomically stable. These will be a useful tool for the study of tumor immunology and genotype-specific cancer biology.

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Transcriptome sequencing of melanocytic nevi and melanomas from Grm1 transgenic mice to determine melanoma driver mutations

Cited by 4 publications

References 12 publications

Selenium-binding protein 1 is down-regulated in malignant melanoma

Selenium-binding protein 1 is down-regulated in malignant melanoma

Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model

The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations

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