Oncogenes in Retroviruses and Cells: Biochemistry and Molecular Genetics

Bister, Klaus; Jansen, H W

doi:10.1016/s0065-230x(08)60199-2

Cited by 83 publications

(62 citation statements)

References 499 publications

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“…In these parameters, they surpass cells transformed by a single oncogene, like the v-myc oncogene of avian acute leukemia virus MC29, or the v-mil or v-jun oncogene, carried by retroviral constructs (Figure 1a and b). To elucidate the molecular mechanisms underlying the high oncogenic potential of MH2 both in vitro and in vivo (Rapp et al, 1985;Bister and Jansen, 1986;Graf et al, 1986), we used comparative gene expression analyses to identify genes specifically activated in v-myc/v-miltransformed quail embryo fibroblasts.…”

Section: Resultsmentioning

confidence: 99%

“…There is clear evidence that Myc and Mil(Raf) act synergistically in cell transformation. The strikingly high oncogenic potential of avian leukemia and carcinoma virus MH2 (Bister and Jansen, 1986;Graf et al, 1986) and of its constructed murine counterpart J2 (Rapp et al, 1985) is apparently due to the combination of the v-myc and v-mil(raf) oncogenes in one retroviral genome leading to concomitant highlevel expression of the v-Myc and v-Mil(Raf) oncoproteins. However, v-Myc expression does not lead to increased c-Mil protein levels, and, vice versa, v-Mil does not induce elevated c-Myc levels (cf.…”

Section: Discussionmentioning

confidence: 99%

“…The subsequent discovery of multiple oncogenes in single retroviral genomes, acquired by multiple transductions of cellular proto-oncogenes, provided strong genetic and molecular evidence in support of the notion that oncogenes cooperate in cell transformation and that multiple mutational events enhance tumorigenesis. One of the viruses containing more than one oncogene, avian leukaemia-and carcinoma-inducing retrovirus MH2, carries transduced v-myc and v-mil alleles derived from the cellular protooncogenes c-myc and c-mil, respectively (Jansen et al, 1983a(Jansen et al, , b, 1984Bister and Jansen, 1986). The myc oncogene, originally identified as a single oncogenic determinant (v-myc) in avian acute leukemia virus MC29, encodes a bHLHZip protein (Myc), encompassing protein dimerization (helix-loop-helix, leucine zipper) and DNA contact (basic region) surfaces, that forms heterodimers with the Max protein and binds to specific DNA sequence elements (E-boxes) Duesberg et al, 1977;Blackwell et al, 1990;Blackwood and Eisenman, 1991;Kerkhoff et al, 1991;Dang, 1999;Grandori et al, 2000;Eisenman, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…The c-mil(raf) proto-oncogene encodes the serine/threonine-specific protein kinase c-Mil(Raf) that is an important part of a conserved signalling pathway transducing signals from the cell surface to the nucleus (Bister and Jansen, 1986;Wellbrock et al, 2004). Growth factor binding to cell surface receptors leads to activation of Ras and subsequently of Mil(Raf).…”

Section: Introductionmentioning

confidence: 99%

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Cooperative cell transformation by Myc/Mil(Raf) involves induction of AP-1 and activation of genes implicated in cell motility and metastasis

2006

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cooperative cell transformation by Myc/Mil(Raf) involves induction of AP-1 and activation of genes implicated in cell motility and metastasis

2006

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“…The myc oncogene was originally identified as a transduced allele (v-myc) representing the oncogenic determinant of avian acute leukemia virus MC29 (Bister and Jansen, 1986). Deregulation of the cellular c-myc protooncogene by retroviral transduction, chromosomal translocation, promoter insertion, or gene amplification is involved in animal and human tumorigenesis (Nesbit et al, 1999).…”

Section: Introductionmentioning

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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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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A phase 2 pilot trial of low‐dose, continuous infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma

Bhatt

Merchan

Parker

et al. 2010

Cancer

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BACKGROUND: Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX-2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM. METHODS: Patients received paclitaxel 10 mg/m 2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6-week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study. RESULTS: Twenty patients were enrolled. Twelve of 20 patients (60%) had received 2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment-related grade 3/4 toxicities were limited to catheter-related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43-151 days), and the median overall survival was 212 days (95% confidence interval, 147-811 days). CONCLUSIONS: Low-dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease.

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Oncogenes in Retroviruses and Cells: Biochemistry and Molecular Genetics

Cited by 83 publications

References 499 publications

Cooperative cell transformation by Myc/Mil(Raf) involves induction of AP-1 and activation of genes implicated in cell motility and metastasis

Cooperative cell transformation by Myc/Mil(Raf) involves induction of AP-1 and activation of genes implicated in cell motility and metastasis

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

A phase 2 pilot trial of low‐dose, continuous infusion, or “metronomic” paclitaxel and oral celecoxib in patients with metastatic melanoma

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