Microarray Analysis Detects Novel Pax3 Downstream Target Genes

Mayanil, C. Shekhar; George, David; Freilich, Laura; Miljan, Erik J.; Mania-Farnell, Barbara; McLone, David G.; Bremer, E.

doi:10.1074/jbc.m107933200

Cited by 106 publications

(103 citation statements)

References 48 publications

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“…MEST has been indicated to play a role in muscle differentiation (Yan et al, 2003), and its mRNA expression is high in ARMS (Baer et al, 2004). MEST is a downstream target of PAX3, the gene involved in the PAX3-FKHR fusion that is typical for alveolar rhabdomyosarcomas (Mayanil et al, 2001). It thus appears that the PAX3-FKHR fusion may influence the transcription of miR-335 that has several predicted targets.…”

Section: Synovial Sarcomamentioning

confidence: 99%

MicroRNA expression signature of human sarcomas

et al. 2007

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MicroRNAs (miRNAs) are B22 nucleotide-long noncoding RNAs involved in several biological processes including development, differentiation and proliferation. Recent studies suggest that knowledge of miRNA expression patterns in cancer may have substantial value for diagnostic and prognostic determinations as well as for eventual therapeutic intervention. We performed comprehensive analysis of miRNA expression profiles of 27 sarcomas, 5 normal smooth muscle and 2 normal skeletal muscle tissues using microarray technology and/or small RNA cloning approaches. The miRNA expression profiles are distinct among the tumor types as demonstrated by an unsupervised hierarchical clustering, and unique miRNA expression signatures were identified in each tumor class. Remarkably, the miRNA expression patterns suggested that two of the sarcomas had been misdiagnosed and this was confirmed by reevaluation of the tumors using histopathologic and molecular analyses. Using the cloning approach, we also identified 31 novel miRNAs or other small RNA effectors in the sarcomas and normal skeletal muscle tissues examined. Our data show that different histological types of sarcoma have distinct miRNA expression patterns, reflecting the apparent lineage and differentiation status of the tumors. The identification of unique miRNA signatures in each tumor type may indicate their role in tumorigenesis and may aid in diagnosis of soft tissue sarcomas.

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Section: Synovial Sarcomamentioning

confidence: 99%

MicroRNA expression signature of human sarcomas

et al. 2007

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“…Each oligo is represented in duplicate on every array (http://www.hgmp.mrc.ac.uk/research/microarray). cDNA fluorescently labeled with either Cy3 or Cy5 (Amersham Pharmacia Biotech, Buckinghamshire, UK) was synthesized from 50 lg total RNA by oligo(dT) 15 (Promega) primed polymerization using Superscript II reverse transcriptase (InVitrogen, Paisley, UK) as described by Khan et al 19 The same reference RNA from Melan a-pcDNA4 empty vector transfected cells was used as a control in each hybridization. Control cDNA was labeled with one of the 2 fluorochromes, Cy3 or Cy5, and the test cDNA (from Melan aPAX3c, -PAX3g, or -PAX3e stable transfectants) with the other.…”

Section: Cdna Microarraymentioning

confidence: 99%

“…14 Other targets such as STX, TIMP3, NF-kB, NCAM, MyoD, Dep-1 and Mbp gene have also been reported. 15, 16 Barber et al 17 using a ''cyclic amplification and selection of targets'' (CASTing) strategy identified further PAX3 targets including Itm2A, Fath, FLT1 and TGFa. The genomic DNA near these genes contained PAX3 binding sites, conferring PAX3-dependent regulation.…”

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confidence: 99%

Investigation of downstream target genes of PAX3c, PAX3e and PAX3g isoforms in melanocytes by microarray analysis

Wang

Kumar

Mitsios

et al. 2006

Intl Journal of Cancer

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PAX3 encodes a transcription factor, which with Zic1 is necessary for induction of the neural crest during early embryonic development. There are 7 human PAX3 isoforms (a–h). PAX3e is the full length isoform comprising 10 exons. PAX3c comprises 8 exons plus 5 codons of intron 8, while PAX3g has a truncated transactivation domain. Previous studies by us indicated that these isoforms have different activities in melanocytes in vitro. In this study, a mouse gene oligo array (∼7.5 k oligos), from the Human Genome Mapping Project (HGMP) Resource Centre, was used to screen for alterations in downstream gene expression in PAX3c, PAX3e and PAX3g melanocyte transfectants, compared with empty vector controls. The data analyses identified 109 genes up or downregulated, at least 2‐fold, and involved in cell differentiation, proliferation, migration, adhesion, apoptosis and angiogenesis. Semi‐quantitative RT‐PCR and Western blotting confirmed the changes identified by microarrays for several putative targets of PAX3, including Met, MyoD and Muc18, and previously undescribed targets, including Dhh, Fgf17, Kitl and Rac1. Thus, our data reveal that PAX3 isoforms regulate distinct but overlapping sets of genes in melanocytes in vitro. © 2006 Wiley‐Liss, Inc.

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“…4 Among human tumors, PSA was found in small cell lung cancer (SCLC), 5 non-small cell lung cancer (NSCLC), 6 NB, 7 alveolar rhabdomyosarcoma, 8 Wilm's tumor 9 and medulloblastoma. 10 In 236 patients with NSCLC, PSA expression correlated with stage; 5-year survival was significantly lower for PSA-positive versus negative patients (52.1% versus 71.3%, respectively). 6 Reactivity of PSA-NCAM by immunohistochemistry was highest in patients with undifferentiated NB and advanced stages of the disease.…”

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confidence: 99%

Sialyltransferase STX (ST8SiaII): A novel molecular marker of metastatic neuroblastoma

Cheung

Vickers

Cheung

2006

Intl Journal of Cancer

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Polysialic acid (PSA) is highly expressed in many human cancers, including neuroblastoma (NB), and is critical for cellular adhesion, neuronal migration and tumor metastasis. The key enzyme responsible for PSA synthesis is sialyltransferase STX (ST8SiaII). Using quantitative RT-PCR we (i) studied STX expression in 39 NB tumors and 8 cell lines and (ii) examined its potential clinical utility as an early response marker in the bone marrows of the entire cohort of 136 high-risk NB patients treated with an immunotherapy protocol utilizing anti-GD2 antibody 3F8 and GM-CSF. Based on the quantitation of 24 normal marrow and peripheral blood samples, a normalized STX transcript value below the mean 1 2SD was defined as negative. Sensitivity of this assay was 1 NB cell in 10 6 normal mononuclear cells. STX expression was high among NB tumors of all stages, as well as NB cell lines of different phenotypes. Evaluation for early (2.5 months from protocol entry) marrow response by univariate Cox model indicated that STX marker status (positive versus negative) was strongly associated with both progression-free and overall survival (p < 0.0005 for both). Similarly, the STX transcript level of posttreatment marrows was also highly prognostic of outcome (PFS, p 5 0.001; OS, p < 0.0005). We conclude that STX mRNA has potential clinical utility as a molecular marker of metastatic NB. ' 2006 Wiley-Liss, Inc.

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Microarray Analysis Detects Novel Pax3 Downstream Target Genes

Abstract: Pax3 is a transcription factor that is

Cited by 106 publications

References 48 publications

MicroRNA expression signature of human sarcomas

MicroRNA expression signature of human sarcomas

Investigation of downstream target genes of PAX3c, PAX3e and PAX3g isoforms in melanocytes by microarray analysis

Sialyltransferase STX (ST8SiaII): A novel molecular marker of metastatic neuroblastoma

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