Toxicogenomics of A375 Human Malignant Melanoma Cells

Cheng, Sun-Long; Liu, Rosa Huang; Sheu, Jin-Nan; Chen, Shui‐Tein; Sinchaikul, Supachok; Tsay, Gregory J.

doi:10.2217/14622416.8.8.1017

Cited by 12 publications

(17 citation statements)

References 97 publications

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“…The human malignant melanoma cell line A375 contains the BRAF V600E mutation and has constitutively elevated ERK activity, which is required for its proliferation (Cheng et al., 2007). We demonstrated that ectopic expression of DUSP6 in A375 cells dephosphorylated ERK.…”

Section: Discussionmentioning

confidence: 99%

Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype

Song

Ritchie

et al. 2012

Pigment Cell Melanoma Res

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Subscribe to PCMR and stay up-to-date with the only journal committed to publishing basic research in melanoma and pigment cell biology As a member of the IFPCS or the SMR you automatically get online access to PCMR. Sign up as a member today at www.ifpcs.org or at www.societymelanomaresarch.org SummaryThe mitogen-activated protein kinase (MAPK) pathway is important in melanoma. In this pathway, DUSP6 phosphatase negatively controls the activation of extracellular signal-regulated (ERK) kinase. Through comparison of melanoma signalling pathways between immortal mouse melanocytes and their tumourigenic derivatives, retrieved from mouse xenografts, we identified a molecularly distinct subtype of melanoma, characterized by reduced ERK activity and increased DUSP6 expression. Overexpression of DUSP6 enhanced anchorage-independent growth and invasive ability of immortal mouse melanocytes, suggesting that increased DUSP6 expression contributes to melanoma formation in the mouse xenografts. In contrast, reduced tumourigenicity was observed after DUSP6 overexpression in human melanoma cells. A minority of thick human primary melanomas had high DUSP6 expression and the same poor melanoma-specific survival as the majority of thick primaries with low DUSP6 levels. We have demonstrated that DUSP6 is important in melanoma and that it plays a different role in our distinct subtype of mouse melanoma compared with that in classic human melanoma.

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Section: Discussionmentioning

confidence: 99%

Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype

Song

Ritchie

et al. 2012

Pigment Cell Melanoma Res

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“…However, the contribution of FGFR3 and CD82 to melanoma metastasis may largely be mediated indirectly through downstream effectors of FGFR3, such as members of the Ras/Raf/mitogenactivated protein kinase pathway (24), which may be regulated by BRAF (25). Down-regulation of CD82 is observed in the advanced stages of a wide variety of cancers including skin (26).…”

Section: Ref 18)mentioning

confidence: 99%

Detection of Copy Number Alterations in Metastatic Melanoma by a DNA FluorescenceIn situHybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431)

Moore

Persons

Sosman

et al. 2008

Clinical Cancer Research

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Purpose: Gene copy number alteration (CNA) is common in malignant melanoma and is associated with tumor development and progression. The concordance between molecular cytogenetic techniques used to determine CNA has not been evaluated on a large set of loci in malignant melanoma. Experimental Design: A panel of 16 locus-specific fluorescence in situ hybridization (FISH) probes located on eight chromosomes was used to identify CNA in touch preparations of frozen tissue samples from 19 patients with metastatic melanoma (SWOG-9431). A subset (n = 11) was analyzed using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) of DNA isolated directly from touch-preparation slides. Results: By FISH, most samples showed loss near or at WISP3/6p21, CCND3/6q22, and CDKN2A/9p21 (>75% of samples tested). More than one third of CDKN2A/9p21 losses were biallelic. Gains of NEDD9/6p24, MET/7q31, and MYC/8q24 were common (57%, 47%, and 41%, respectively) and CNA events involving 9p21/7p12.3 and MET were frequently coincident, suggesting gain of the whole chromosome 7. Changes were confirmed by aCGH, which also uncovered many discreet regions of change, larger than a single BAC. Overlapping segments observed in >45% of samples included many of the loci analyzed in the FISH study, in addition to other WNT pathway members, and genes associated withTP53 pathways and DNA damage response, repair, and stability. Conclusions: This study outlines a set of CNAs at the gene and regional level, using FISH and aCGH, which may provide a benchmark for future studies and may be important in selection of individual therapy for patients with metastatic malignant melanoma.Skin cancer occurs in more than 1,200,000 Americans annually (1). Most cases are highly curable squamous and basal cell cancers, but f62,500 new cases of melanoma will be diagnosed this year in the United States. The incidence of melanoma has steadily been increasing, and melanoma causes more than 8,400 deaths per year in this country, accounting for the vast majority of skin cancer deaths (1). Early detection and surgery are key to improved survival. Once metastatic melanoma is diagnosed, median survival duration of only 6 to 9 months is expected.Primary melanoma lesions have largely been characterized by Breslow's depth, Clark's level, ulceration, microscopic involvement of regional lymph nodes, as well as mitotic index, lymphocyte infiltration, and signs of regression. Metastatic melanoma is staged based on location of lesions, such as skin, lymph nodes, lung, liver, and other organ sites, and finally, serum lactate dehydrogenase. With advances in genetic technology, new tools have been developed that may facilitate the collection of a set of potentially robust prognostic genetic indicators (2, 3) to augment the anatomic classifications.Cytogenetic, molecular, and biological studies indicate that multiple genetic alterations are involved in the development and progression of malignant melanoma, with several genes and chromosomal sites del...

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“…Toxicogenomics tools were used to study the genotoxic effect of active compounds on the gene-expression profile of A375 human malignant melanoma cells, through the other molecular functions of target genes, regulatory pathways and mechanisms of malignant melanomas. It also includes the current systems biology approaches, which are very useful for analyzing the biological system and understanding the entire mechanisms of malignant melanomas [20] . Fractal analytical approach in cancer cell investigation provided meaningful insights into the relationships between morphology and phenotype.…”

Section: Immunology Of Toxicogenomicsmentioning

confidence: 99%

Toxicogenomics and Its Application in Cancer Pathogenesis

RA¹,

SS²,

VS³

2010

Int J Med Clin Res

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Toxicology, the study of poisons, focuses on substances and treatments that cause adverse effects in living things. A critical part of this study is the characterization of the adverse effects at the level of the organism, the tissue, the cell, and the molecular makeup of the cell. Thus, Toxicology traditionally has focused on phenotypic changes in an organism that result from exposure to chemical, physical, or biologic agents. Such changes range from reversible effects, such as transient skin reactions, to chronic diseases, such as cancer, to the extreme end point of death. Typical whole-animal toxicology studies may range from single-dose acute to chronic lifetime exposures, and they include assessments of end points such as clinical signs of toxicity, body and organ weight changes, clinical chemistry, and histopathologic responses. INTRODUCTIONToxicogenomic technologies comprise several different technology platforms for analysis of genomes, transcripts, proteins, and metabolites. It is important to recognize two additional issues associated with the use of toxicogenomic technologies. First, the large quantity of information that a single experiment can generate, and the comprehensive nature of this information, is much greater than what traditional experiments generate. Second, the advancement of computing power and techniques enable these large amounts of information to be synthesized from different sources and experiments and to be analyzed in novel ways [1]. Genomic technologies encompass both genome sequencing technologies, which derive DNA sequences from genes and other regions of DNA, and genotype analysis, which detects sequence variations between individuals in individual genes. The convergence of genome sequencing and genotyping technologies will eventually enable whole-genome sequences of individuals to be analyzed [2]. Transcriptomic technologies (or gene expression profiling) measure mRNA expression in a highly parallel assay system, usually using microarrays. As the first widely available method for global analysis of gene expression, DNA microarrays are the emblematic technology of the post-genomic era. Microarray technology for transcriptomics has enabled the analysis of complex, multigene systems and their responses to environmental perturbations [3]. Proteomics is the study of collections of proteins in living systems. Because the same proteins may exist in multiple modified and variant forms, proteomes are more complex than the genomes and transcriptomes that encode them. Proteomic technologies use mass spectrometry (MS) and microarray technologies to resolve and identify the components of complex protein mixtures, to identify and map protein modifications, to characterize protein functional associations, and to compare proteomic changes quantitatively in different biologic states [4]. Bioinformatics is a branch of computational biology focused on applying advanced computational techniques to the collection, management, and analysis of numerical biologic data. Elements of bioinfor...

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Toxicogenomics of A375 Human Malignant Melanoma Cells

Cited by 12 publications

References 97 publications

Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype

Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype

Detection of Copy Number Alterations in Metastatic Melanoma by a DNA FluorescenceIn situHybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431)

Toxicogenomics and Its Application in Cancer Pathogenesis

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