Zebrafish as a Platform to Study Tumor Progression
The zebrafish has emerged as a powerful model system to study human diseases, including a variety of neoplasms. Principal components that have contributed to the rise in use of this vertebrate model system are its high fecundity, ease of genetic manipulation, and low cost of maintenance. Vital imaging of the zebrafish is possible from the transparent embryonic stage through adulthood, the latter enabled by a number of mutant lines that ablate pigmentation. As a result, high-resolution analyses of tumor progression can be accomplished in vivo. Straightforward transgenesis of zebrafish has been employed to develop numerous tumor models that recapitulate many aspects of human neoplastic disease, both in terms of pathologic and molecular conservation. The small size of zebrafish embryos has enabled screens for novel chemotherapeutic agents. Its facile genetics have been exploited in studies that extend beyond modeling cancer to investigations that define new cancer genes and mechanisms of cancer progression. Together, these attributes have established the zebrafish as a robust and versatile model system for investigating cancer. In this chapter we describe methods that are used to study a gene’s impact on melanoma progression. We detail methods for making transgenic animals and screening for tumor onset as well as methods to investigate tumor invasion and propagation.
Key wordsDanio rerio Zebrafish Melanoma Melanocyte BRAF p53 Tumor progression
The authors thank Dr. Yariv Houvras for his contributions in developing miniCoopR-based screening. This work was supported by NIH Pathway to Independence (R00AR056899-03) and American Cancer Society Research Scholar (RSG-12-150-01-DDC) awards to C.C. and a Cancer Research Institute Irvington Fellowship to C.A.P.
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