1) Ewing's Sarcoma. Within the preceding year we have shown that zebrafish with EWS/FLI1 leads to mitotic defects with abnormal or multipolar mitotic spindles starting from the bud stage (10hpf). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. 2) Ovarian cancer. We have iidentified zebrafish harboring mutations in the zebrafish BRCA-2 gene. Zebrafish with homozygous mutation of brca2 fail to develop ovaries. However, they develop gonadal tumors over time, a process enhanced with loss of p53.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010549-10
Application #
8552731
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2012
Total Cost
$811,990
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Shive, Heather R; West, Robert R; Embree, Lisa J et al. (2015) Expression of KRASG12V in Zebrafish Gills Induces Hyperplasia and CXCL8-Associated Inflammation. Zebrafish 12:221-9
Shive, Heather R; West, Robert R; Embree, Lisa J et al. (2014) BRCA2 and TP53 collaborate in tumorigenesis in zebrafish. PLoS One 9:e87177
English, Milton A; Lei, Lin; Blake, Trevor et al. (2012) Incomplete splicing, cell division defects, and hematopoietic blockage in dhx8 mutant zebrafish. Dev Dyn 241:879-89
Shive, Heather R; West, Robert R; Embree, Lisa J et al. (2010) brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. Proc Natl Acad Sci U S A 107:19350-5
Hickstein, Dennis D; West, Robert R (2010) A WHIM-sical zebrafish. Blood 116:2621-2