Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep41280
Title: Males develop faster and more severe hepatocellular carcinoma than females in kras V12 transgenic zebrafish
Authors: Li Y. 
Li H.
Spitsbergen J.M.
Gong Z. 
Keywords: beta catenin
cadherin
doxycycline
Kras protein, zebrafish
protein p21
zebrafish protein
animal
carcinogenesis
cell proliferation
disease exacerbation
female
genetics
liver cell carcinoma
liver tumor
male
metabolism
oncogene
pathology
transgenic animal
zebra fish
Animals
Animals, Genetically Modified
beta Catenin
Cadherins
Carcinogenesis
Carcinoma, Hepatocellular
Cell Proliferation
Disease Progression
Doxycycline
Female
Liver Neoplasms
Male
Oncogenes
Proto-Oncogene Proteins p21(ras)
Zebrafish
Zebrafish Proteins
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Li Y., Li H., Spitsbergen J.M., Gong Z. (2017). Males develop faster and more severe hepatocellular carcinoma than females in kras V12 transgenic zebrafish. Scientific Reports 7 : 41280. ScholarBank@NUS Repository. https://doi.org/10.1038/srep41280
Abstract: Hepatocellular carcinoma (HCC) is more prevalent in men than women, but the reason for this gender disparity is not well understood. To investigate whether zebrafish could be used to study the gender disparity of HCC, we compared the difference of liver tumorigenesis between female and male fish during early tumorigenesis and long-term tumor progression in our previously established inducible and reversible HCC model - the kras V12 transgenic zebrafish. We found that male fish developed HCC faster than females. The male tumors were more severe from the initiation stage, characteristic of higher proliferation, activation of WNT/?-catenin pathway and loss of cell adhesion. During long-term tumor progression, the male tumors developed into more advanced multi-nodular tumors, whereas the female tumors remain uniform and homogenous. Moreover, regression of male tumors required longer time. We further investigated the role of sex hormones in kras V12 transgenic fish. Estrogen treatment showed tumor suppressing effect during early tumorigenesis through inhibiting cell proliferation, whereas androgen accelerated tumor growth by promoting cell proliferation. Overall, our study presented the zebrafish as a useful animal model for study of gender disparity of HCC. © The Author(s) 2017.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174498
ISSN: 2045-2322
DOI: 10.1038/srep41280
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