Novel MITF targets identified using a two‐step DNA microarray strategy

@article{Hoek2008NovelMT,
  title={Novel MITF targets identified using a two‐step DNA microarray strategy},
  author={Keith S. Hoek and Natalie C. Schlegel and Ossia M. Eichhoff and Daniel S. Widmer and Christian Praetorius and Steingr{\'i}mur Einarsson and Sigr{\'i}dur Valgeirsd{\'o}ttir and Kristin Bergsteinsdottir and Alexander Schepsky and Reinhard Dummer and Eir{\'i}kur Steingr{\'i}msson},
  journal={Pigment Cell \& Melanoma Research},
  year={2008},
  volume={21}
}
Malignant melanoma is a chemotherapy‐resistant cancer with high mortality. Recent advances in our understanding of the disease at the molecular level have indicated that it shares many characteristics with developmental precursors to melanocytes, the mature pigment‐producing cells of the skin and hair follicles. The development of melanocytes absolutely depends on the action of the microphthalmia‐associated transcription factor (MITF). MITF has been shown to regulate a broad variety of genes… 
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TLDR
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References

SHOWING 1-10 OF 103 REFERENCES
Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma
TLDR
It is suggested that MITF represents a distinct class of ‘ lineage survival’ or ‘lineage addiction’ oncogenes required for both tissue-specific cancer development and tumour progression, and Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm.
Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.
TLDR
A model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodelling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling is suggested.
Identification of Aim-1 as the underwhiteMouse Mutant and Its Transcriptional Regulation by MITF*
TLDR
It is shown that the mouse homolog of a recently identified gene whose mutation produces Japanese gold-colored fish maps to the mouseunderwhite locus, and evidence that AIM-1 is transcriptionally modulated by MITF, a melanocyte-specific transcription factor essential to pigmentation and a clinical diagnostic marker in human melanoma is provided.
Transcriptional Regulation of the Melanoma Prognostic Marker Melastatin (TRPM1) by MITF in Melanocytes and Melanoma
TLDR
These studies identify MITF as a major transcriptional regulator of TRPM1 and suggest that its prognostic value may be linked to MITF-mediated regulation of cellular differentiation.
Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays
TLDR
The genes that were previously found to be differentially expressed in human melanoma cell lines 1F6 and Mel57 could be potent targets for diagnostic, prognostic and/or therapeutic interventions.
Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes.
TLDR
It is proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.
Gpnmb is a melanoblast‐expressed, MITF‐dependent gene
TLDR
A whole genome annotation of 2,460,048 consensus MITF binding sites was performed, and cross‐referenced this with evolutionarily conserved genomic sequences at the GPNMB locus, indicating a significant role for this site in Gpnmb transcriptional regulation.
Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression
TLDR
It is shown that Mitf can act as a novel anti-proliferative transcription factor able to induce a G1 cell-cycle arrest that is dependent on Mitf-mediated activation of the p21Cip1 (CDKN1A) cyclin-dependent kinase inhibitor gene.
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