Biology of human melanoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE17275 | GEO | 2011/10/31
SECONDARY ACCESSION(S): PRJNA119137
REPOSITORIES: GEO
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Project description:In normal skin, interactions between melanocytes and keratinocytes, and between melanocytes and the basal membrane are functionally relevant for maintenance of homeostasis and epidermal melanin unit whose deregulation may trigger a continuous proliferation of the melanocytes. In order to further elucidate the molecular events related to cell-cell and cell-ECM interactions in relation to the biology of melanomas, we analyzed the expression profile of 64 human melanomas, 21 primary samples and 43 independent metastasis. Tissue samples melanomas were obtained at Hospital A. C. Camargo. All patients signed an informed consent and the study was approved by our internal ethics committee. Tissue samples obtained by surgery were snap-frozen in liquid nitrogen and biopsy samples were collected in RNAlaterTM (Ambion, Austin, TX). Non-tumor areas were removed by handy dissection and only samples represented by at least 70% of tumors cells within their natural stroma were selected for RNA extraction. Total RNA was extracted using RNeasy Midi-Kit® and amplified by a T7-based protocol. An indirect cDNA-labeling was performed as described by Cox et al. (2004). We used dual-label system in which two RNA samples (test and reference) were separately reverse-transcribed, labeled, mixed, and hybridized together to each array. Each sample was hybridized in duplicate, with dye swap between sample and reference. As reference RNA we used a pool of equal amounts of total RNA from 5 human cutaneous melanoma cell lines (SK-MEL 05; 17; 28; 37 and 188, kindly provided by Dr. Alan Houghton, MSKCC, New York, NY, USA). We used glass arrays containing 4.800 cDNA sequences (Brentani et al. 2003) were prepared in our lab with the aid of the Flexys robot17 (Genomic Solutions, Cambridgeshire, United Kingdom). The list of immobilized genes can be obtained at GEO, accession number GPL1930. Pre-hybridization, hybridization and washing were performed as previously described (Gomes et al. 2003; 2005), and slides were scanned on a laser scanner (ScanArray Express, PerkinElmer Life Sciences, Boston, MA). Data were extracted with ScanArray Express software (PerkinElmer Life Sciences, Boston, MA) using the histogram method.
2011-10-31 | E-GEOD-17275 | biostudies-arrayexpress
Project description:Melanogenesis is the biological process regulating the synthesis of melanin pigments in melanocytes. Defective melanogenesis is associated with numerous human skin diseases, including, but not limited to, albinism, vitiligo, melasma, hypo- and hyperpigmentation disorders. Tyrosinase is the rate-limiting enzyme controlling melanogenesis, and hence tremendous efforts have been made to identify potent and safe inhibitors of tyrosinase function. Such inhibitors would also have potential as cancer therapies; melanomas are derived via malignant transformation of melanocytes, and inhibition of tyrosinase activity and/or melanogenesis has been suggested as a possible therapeutic strategy. However, despite decades of research, there is currently no effective treatment that inhibits melanogenesis or tyrosinase activity with no adverse side effects. In this study, we report characterization of the ML233 chemical as a potent inhibitor of tyrosinase activity in vivo and in vitro. We demonstrated that ML233 reduces melanin production in the zebrafish model with no observable significant toxic side effects, and in murine melanoma cells. We also showed that these effects are likely mediated through direct tyrosinase-ML233 interaction, i.e., binding of the ML233 molecule to the active site of the protein to inhibit its function. In addition, we showed that ML233 has the capacity to limit melanoma-cell proliferation in patient-derived xenograft organoids. Together, our results reveal that ML233 plays a dual role via inhibition of both melanin production and melanoma proliferation, and that ML233-mediated tyrosinase inhibition is a potentially safe and effective approach to alleviate the symptoms of melanocyte-associated diseases and thereby substantially improve human health.
2024-05-22 | GSE268076 | GEO
Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages. Skin epidermal cells from 2 individual C57BL/6 mice and 2 individual AhR-deficient mice (deletion of exon2, AhRtm1Bra) were grown for 6-8 weeks in selection medium to propagate melanocytes.
2010-09-05 | E-GEOD-19411 | biostudies-arrayexpress
Project description:We report the gene expression comparison of zebrafish melanocytes and melanomas. These comparisons were used for integrative genomic studies that identified the BMP factor GDF6 as a new oncogene that is specifically expressed in melanomas.
2018-02-14 | GSE83399 | GEO
Project description:We report the gene expression comparison of zebrafish melanocytes and melanomas. These comparisons were used for integrative genomic studies that identified the BMP factor GDF6 as a new oncogene that is specifically expressed in melanomas.
2018-02-14 | GSE83343 | GEO
Project description:Lineage-specific differentiation programs are activated by epigenetic changes in chromatin structure. Melanin-producing melanocytes maintain a gene expression program ensuring appropriate enzymatic conversion of metabolites into the pigment, melanin, and its transfer to surrounding cells. During neuroectodermal development, SMARCA4, the catalytic subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes, is essential for lineage specification. SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment-producing melanocytes. In addition to the catalytic domain, SMARCA4 and several SWI/SNF subunits contain bromodomains which are amenable to pharmacological inhibition. We investigated the effects of pharmacological inhibitors of SWI/SNF bromodomains on melanocyte differentiation. Strikingly, treatment of murine melanoblasts and human neonatal epidermal melanocytes with selected bromodomain inhibitors abrogated melanin synthesis and visible pigmentation. Using functional genomics, iBRD9, a small molecule selective for the bromodomain of BRD9, repressed pigmentation-specific gene expression. Depletion of BRD9 confirmed a requirement for expression of pigmentation genes in the differentiation program from melanoblasts into pigmented melanocytes and in melanoma cells. Chromatin immunoprecipitation assays showed that iBRD9 disrupts the occupancy of bromodomain containing 9 (BRD9) and the catalytic subunit SMARCA4. These data indicate that BRD9 promotes melanocyte differentiation and pigmentation whereas pharmacological inhibition of BRD9 is repressive.
2022-10-17 | GSE210015 | GEO
Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages.
2010-09-05 | GSE19411 | GEO
Project description:Immortalized, amelanotic melanocytes isolted from skin of Balb/c express enzymatically-inactive tyrosinase due to a homozygous point mutation (TGT->TCT) in tyrosinase gene, resulting in a lack of melanin . To serve as a control cell line, pigmentation was restored in these cells by correcting the point mutation using an RNA-DNA oligonucleotide (kingly gift from Dr. Alexeev Y. Vitali). We used microarray to detail the effect of tyrosinase mutation on gene expression in normal versus mutant melanocytes. Pigmented and non-pigmented melanocytes were grown for RNA extraction and hybridization on Affymetrix microarrays. We used both normal and mutant melanocyte in order to obtain expression profiles. We then examined variances in gene expression between the two cell lines.
2013-09-21 | E-GEOD-51073 | biostudies-arrayexpress
Project description:We report single cell transcriptomes from human skin samples that have been enriched for melanocytes using FACS. This work revealed anatomical site-specific melanocyte expression programs. In addition, by surveying melanocytes at different stages of development, we identified development-associated expression programs that are reflected in the dedifferentiation of melanomas.
2020-05-29 | GSE151091 | GEO
Project description:Spotted oligonucleotide microarrays were used to assess global differential gene expression comparing normal human melanocytes with six independent melanoma cell strains from advanced lesions. The data, validated at the protein level for selected genes, confirmed the overexpression in melanoma cells relative to normal melanocytes of several genes in the growth factor/receptor family that confer growth advantage and metastasis. In addition, novel pathways and patterns of associated expression in melanoma cells not reported before emerged. Six melanoma cultures and two melanocyte cultures. The melanoma cultures are considered, for the purposes of this investigation, replicates from the point of view that they are all melanomas. Three of the melanomas were replicated once or twice in addition.
2010-07-01 | E-GEOD-4576 | biostudies-arrayexpress