Retroviral Mutagenesis of Cellular Oncogenes: A Review with Insights into the Mechanisms of Insertional Activation

Kung, Hsing-Jien; Boerkoel, Cornelius F.; Carter, T. H.

doi:10.1007/978-3-642-76524-7_1

Cited by 86 publications

(81 citation statements)

References 163 publications

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“…Replication-competent MuLV induce neoplastic disease in a reproducible manner through a process known as insertional mutagenesis, the subject of exhaustive discussion in several excellent reviews, 36,[46][47][48][49][50][51][52][53] and here briefly. Its success in contributing to our knowledge of the genetic basis of myeloid disease resulted in the development of constructive models of several AML subtypes, [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] which are summarised in Table 1.…”

Section: Insertional Mutagenesismentioning

confidence: 99%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

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From the early inception of the transplant models through to contemporary genetic and xenograft models, evolution of murine leukaemic model systems have been critical to our general comprehension and treatment of cancer, and, more specifically, disease states such as acute myelogenous leukaemia (AML). However, even with modern advances in therapeutics and molecular diagnostics, the majority of AML patients die from their disease. Thus, in the absence of definitive in vitro models which precisely recapitulate the in vivo setting of human AMLs and failure of significant numbers of new drugs late in clinical trials, it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. While various model systems are described and discussed in the literature from initial transplant models such as BNML and spontaneous murine leukaemia virus models, to the more definitive genetic and clinically significant NOD/SCID xenograft models, there exists no single compendium which directly assesses, reviews or compares the relevance of these models. Thus, the function of this article is to provide clinicians and experimentalists a chronological, comprehensive appraisal of all AML model systems, critical discussion on the elucidation of their roles in our understanding of AML and consideration to their efficacy in the development of AML chemotherapeutics.

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Section: Insertional Mutagenesismentioning

confidence: 99%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

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“…This approach was based on the random integration of proviruses into the host cell genome, thereby activating or inactivating cellular genes depending on the site of integration. The use of retroviral insertional mutagenesis has previously been shown to be e ective in the identi®cation of oncogenes and tumor suppressor genes in various animal tumor systems induced by slow transforming retroviruses (Kung et al, 1991;Peters, 1986).…”

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confidence: 99%

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

et al. 2000

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A major obstacle in the systemic treatment of advanced malignant melanoma is its intrinsic resistance to conventionally used chemotherapeutic agents. In order to investigate the mechanisms of this intrinsic resistance, we have previously utilized retroviral insertional mutagenesis on an early-stage, drug sensitive human melanoma cell line (WM35) to establish mutated cell lines that exhibited increased resistance to cis-diamminedichloroplatinum(II) (CDDP). Here, we demonstrate that this increased resistance to CDDP is mediated by the over-expression of tyrosinase-related protein-2 (TYRP2), an enzyme that normally functions in the biosynthesis of the pigment, melanin. Northern and Western blot analyses revealed that the expression of TYRP2 in the virally-derived cell lines as well as in a panel of human melanoma cell lines positively correlated with their levels of resistance to CDDP. Furthermore, enforced expression of TYRP2 in WM35 cells by transfection elevated their resistance to CDDP. The increased CDDP resistance in the virally-derived clones and TYRP2 transfectants was accompanied by a reduction in CDDP-induced apoptosis. Interestingly, the virally-derived CDDP-resistant clones also showed cross resistance to carboplatin and methotrexate, but not taxol, suggesting that TYRP2 over-expression may confer resistance speci®cally to DNA damaging agents.Overall, these results demonstrate a novel mechanism of drug resistance in human melanoma cells that is mediated by the over-expression of TYRP2. Since TYRP2 is expressed only in cells of melanocytic lineage, this may represent the ®rst report of a lineage-speci®c mechanism of drug resistance. In summary, these ®ndings suggest a signi®cant role for TYRP2 in the intrinsic drug resistance phenotype of human melanoma cells and may have important implications in the development of chemosensitization strategies for the clinical management of this disease. Oncogene (2000) 19, 395 ± 402.

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“…All but one of the proviruses were oriented away from the myc gene. The mechanism of cmyc activation in these tumors therefore appears to be by enhancer insertion, as has been previously described for murine T cell lymphomas (reviewed in Kung et al, 1991). A further ®ve tumors had integrations at unidenti®ed loci.…”

Section: Myc Loci Are Frequent Integration Targets In Accelerated Vmymentioning

confidence: 53%

Cooperation of Myb and Myc proteins in T cell lymphomagenesis

1999

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Retroviral Mutagenesis of Cellular Oncogenes: A Review with Insights into the Mechanisms of Insertional Activation

Cited by 86 publications

References 163 publications

Animal models of acute myelogenous leukaemia – development, application and future perspectives

Animal models of acute myelogenous leukaemia – development, application and future perspectives

Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum(II): therapeutic implications

Cooperation of Myb and Myc proteins in T cell lymphomagenesis

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