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The Use of Transgenic Mice in Cancer and Genome Stability Research

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Genome Stability and Human Diseases

Part of the book series: Subcellular Biochemistry ((SCBI,volume 50))

Abstract

The development of effective cancer therapeutics is an important goal of modern biomedical sciences. To identify potential cancer therapeutic targets, the processes involved in tumorigenesis must be understood at all levels, which requires the development of model systems accurately mimicing tumor development. Cancer is the general name given to a variety of complex diseases characterised by uncontrolled cell proliferation. Cancer development is dependent not only on the changes occurring within the transformed cells, but also on the interactions of the cells with their microenvironment. The majority of our current understanding of carcinogenesis comes from the in vitro analysis of late-stage tumor tissue removed from cancer patients. While this has elucidated many genomic changes experienced by cancer cells, it provides little information about the factors influencing early-stage cancer development in vivo. Also certain hallmarks of cancer, such as metastasis and angiogenesis, are impossible to study in vitro. The mouse has become an important model for studying the in vivo aspects of human cancer development. Transgenic mouse models have been engineered to develop cancers, which accurately mimic their human counterparts, and have potential applications to test the effectiveness of novel cancer therapeutics. One of the most promising transgenic mouse models of human cancer arises from mice engineered with genomic instability. These transgenic models have been shown to develop human-like cancers and have the potential to provide insights into the molecular events occurring in earliest stages of tumorigenesis in vivo.

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Abbreviations

Apc:

adenomatous polyposis coli

ATM:

Ataxia-telangiectasia-mutated

CIN:

chromosomal instabilities

Cre/loxP:

recombinase systems (Cre recombinase with loxP recognition site)

DDR:

DNA damage responses

ES:

embryonic stem

FAP:

Familial Adenomatous Polyposis

Flp/FRT:

recombinase systems (Flp recombinase with FRT recognition site)

HR:

homologous recombination

Min:

multiple intestinal neoplasia

MIN:

microsatellite instabilities

NOD/SCID:

non-obese diabetic/severely compromized immunodeficient

OIS:

oncogene-induced senescence

Rb:

retinoblastoma gene (tumor suppressor gene)

SCID:

severely compromized immunodeficient

Terc:

telomerase RNA component also called hTR

TERT:

telomerase reverse transcriptase subunit

TSG:

tumor suppressor gene

tTA:

transcriptional transactivator

WT1:

Wilms’ tumor gene 1

WT1-TCR:

WT1-specific T cell receptor

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Acknowledgment

This work was supported by Health Research Board, Ireland, INTAS, and Science Foundation Ireland. S. C. is an NUIG Scholar.

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Authors and Affiliations

  1. Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, University Rd, Galway, Ireland

    Sarah Conmy & Heinz-Peter Nasheuer

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  1. Sarah Conmy
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  2. Heinz-Peter Nasheuer
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Correspondence to Heinz-Peter Nasheuer .

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  1. Galway, Ireland

    Heinz-Peter Nasheuer

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Conmy, S., Nasheuer, HP. (2010). The Use of Transgenic Mice in Cancer and Genome Stability Research. In: Nasheuer, HP. (eds) Genome Stability and Human Diseases. Subcellular Biochemistry, vol 50. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3471-7_17

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