<i>nmb</i>, a novel gene, is expressed in low‐metastatic human melanoma cell lines and xenografts

Weterman, Marian A. J.; Ajubi, N.E.; Dinter, I.M.R. van; Degen, W.G.J.; Muijen, G.N.P. van; Ruiter, Dirk J.; Bloemers, H. P. J.

doi:10.1002/ijc.2910600111

Cited by 228 publications

(204 citation statements)

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“…The sequence similarities, the shared domain topography, and the common biochemical properties reported for Pmel17 and Mmp115 (Theos et al, 2005) suggest that Pmel17 is indeed the human homolog of the closely related avian WS5 and Mmp115 proteins. The WS5 protein also displays 24% sequence identity (not shown) with the WS5, a direct transcriptional target of Myc F Reiter et al human transmembrane glycoprotein GPNMB that is expressed in most metastatic melanoma cells and has been implicated in the progression of several human malignancies (Weterman et al, 1995).…”

Section: Specific Expression Of Ws5 In Myc-transformed Avian Fibroblastsmentioning

confidence: 99%

“…The Pmel17 gene is normally regulated by the melanocyte-specific bHLHZip microphthalmia-associated transcription factor (MITF) that has DNA-binding specificities similar to those of MycMax (Du et al, 2003). The WS5 protein also shows sequence identity (24%) to another human type I transmembrane glycoprotein, GPNMB (or osteoactivin) (Weterman et al, 1995), that is overexpressed in most metastatic melanoma cells, but also in cancers of the brain, breast, liver, stomach and pancreas. Furthermore, GPNMB was directly shown to be involved in tumor cell invasion and metastasis (Rich et al, 2003).…”

Section: Ws5 a Direct Transcriptional Target Of Mycmentioning

confidence: 99%

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WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

et al. 2006

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We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and a binding site for transcription factor C/EBPa. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPa bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPa-binding site are essential for strong transcriptional activation, and that Myc and C/EBPa synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.

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Section: Specific Expression Of Ws5 In Myc-transformed Avian Fibroblastsmentioning

confidence: 99%

Section: Ws5 a Direct Transcriptional Target Of Mycmentioning

confidence: 99%

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

et al. 2006

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“…DNA samples (50 \xg) were electrophoresed in vertical 1 % agarose gels ( figure 4) from the human calcyclin gene, they were used as probes in mapping the DNase I hypersensitive regions. pMW l is a pUC18 derived vector containing the entire calcyclin coding region in a 362 bp cDNA fragment [14].…”

Section: Methodsmentioning

confidence: 99%

“…The expression of calcyclin was at least ten times elevated in the highly metastatic human cell lines BLM and MV3 as compared to the poorly metas tatic cell lines 530 and 1F6 (see Figure 1A). Correspondingly, a slight amplification of the calcyclin gene in the highly metastatic cell lines was reported although this could not directly account for the differences at the RNA level [14], The present study was undertaken to gain more insight in the regulation of the human calcyclin gene. With this purpose, we examined the expression profile in a number of human tissues and analyzed flanking sequences of the calcyclin promoter for enhancer activity in a panel of human melanoma cell lines with different metastatic behavior.…”

mentioning

confidence: 92%

“…By applying the differential hybridization technique to two subsequent stages of melanocytic tumor progression to identify new progression markers for human cutaneous melanoma, several differentially expressed clones were isolated, one of which appeared to be coding for calcyclin [14]. The expression of calcyclin was at least ten times elevated in the highly metastatic human cell lines BLM and MV3 as compared to the poorly metas tatic cell lines 530 and 1F6 (see Figure 1A).…”

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confidence: 99%

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Functional Analysis of the Human Calcyclin Gene Promoter in a Panel of Human Melanoma Cell Lines

Groningen

Weterman

Swart

et al. 1995

Biochemical and Biophysical Research Communications

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By comparing two subsequent human tumor stages we previously described calcyclin as a new potential melanoma associated neoplastic progression marker positively linked with metastasis. In this study the calcyclin expression levels in a representative panel of human melanoma cell lines were correlated with the occurrence of DNase I hypersensitive (DH) regions and potential enhancer elements in a 6 kb genomic fragment spanning the human calcyclin gene. Examination of the chromatin structure of the transcription unit revealed no qualitative differences in DH sites within the panel of tested human melanoma cells, but especially the sequences around the transcription start site and a 1.5 kb upstream region appeared more accessible to the nuclease in frequently (BLM, MV3) as compared to poorly (530, 1F6) metastasizing cells. The genomic fragments that harbor one or more DH sites were subjected to functional analysis by luciferase reporter gene assays. Thus, an enhancer element was detected between 361 and 167 bp upstream of the transcription start site. This enhancer displayed equal activating potential (2-3 fold) both in weakly and in frequently metastasizing cells and was apparently recognized by transcription factors present in both types of human melanoma cell lines. We. conclude that, in addition to a slight amplification of the encoding gene, the elevated calcyclin mRNA levels are only reflected in a selectively increased accessibility of the chromatin structure to DNasel in metastasizing melanoma cells © 1995 Academic Preas, Inc.Calcyclin is a small calcium-binding protein (10.5 kD) belonging to the SI00 family containing two calcium-binding structures, the so called EF hands. It was identified as a differentially expressed mRNA in serum-stimulated and quiescent fibro blasts [1,2] and was originally isolated from Gr specific temperature sensitive mutants of baby Syrian hamster kidney cells [3].Although the function of calcyclin is still unknown, several observations can be made: the calcyclin gene was induced by serum, platelet-derived growth factor, or epidermal growth factor [1,4,5]. The gene product was shown to bind both zinc and calcium [6] which indicated that it is involved in processes related to signal transduction.

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Expression ofnma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts

et al. 1996

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Metastatic melanoma is one of the most invasive cancers, the incidence of which has rapidly increased in the past decade. The process of metastasis is thought to be characterized by subsequent distinct stages as defined by Clark et at. (1984) and Hcrlyn et ul. (1987), and cventually cnablcs a primary tumor to sprcad and colonize at sccondary sites. A sct of biological markers defining unequivocally each stage of tumor development is lacking. New markers are thus sought for better diagnosis and therapeutic strategies. They may also lead to a better understanding of the tumor biology of melanoma.In cultured human melanocytic cells, several tumor markers have been defined that are possibly indicative for metastatic potential (Wcterman et al., 1994). Some of these markers may be vcry useful in clinical practice as wcll as in studies of tumor biology. Several strategies have been used to isolate tumor progression markers. The use of monoclonal antibodies (MAbs). in particular, was successful in the isolation of membrane associated proteins, such as membrane receptors and adhesion molecules (Real et al., 1985). A number of melanoma markers represent (potential) tumor suppressor activities, e.g., nm23 (Leone et uL, 1091) andpZ6 (Kamb el al., 1994).In the last few ycars, we have idcntified scveral potcntial progression markers, e.g., calcyclin (Weterman et ul., 1992), thymosin-pl0 (Weterman et al., 1993), nmb (Weterman et al., 1995 and nma (this report), by using differential and subtractive hybridization techniques. Calcyclin and thymosin-pl0 are expressed in highly metastatic human melanoma cell lines: whereas nrna and nrnb are expressed in poorly metastatic human melanoma cell lines.Thc absence of cxpression of nrna and nmb in highly metastatic ccll lines docs not imply a rolc in tumor progrcssion, It merely indicates that these markers are part of the phenotype of a non-metastasizing cell line. Because this phenotype may be relevant for tumor biology, we now present a characterization of the nma gene. MATERIAL AND METHODS Biological ma teria IsHuman melanoma cell lines 1F6,530, BLM, MV3 and MV1 (van Muijen et al., 1991a, b, c ) were cultured as described by Weterman et al. (1992). In this pancl of ccll lincs, BLM and MV3 reprcscnt thc highly metastatic cell lines, i.e., those i n which metastases occur in more than 50% of the tumorbearing mice. 1F6, 530 and MV1 produced metastases in less than 10% of the tumor-bearing mice, representing the poorly metastatic cell lines (van Muijen et al., 1 9 9 1~) ; 3 X lo6 cells were used for S.C. inoculation into nude mice (nulmu BALB/c; Bomholtgaard, Ry, Denmark). Excision and processing of the human tissues was pcrformcd as described by Weterman et al. (1995).

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nmb, a novel gene, is expressed in low‐metastatic human melanoma cell lines and xenografts

Cited by 228 publications

References 24 publications

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

Functional Analysis of the Human Calcyclin Gene Promoter in a Panel of Human Melanoma Cell Lines

Expression ofnma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts

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