PUBLICATION
Males develop faster and more severe hepatocellular carcinoma than females in krasV12 transgenic zebrafish.
- Authors
- Li, Y., Li, H., Spitsbergen, J.M., Gong, Z.
- ID
- ZDB-PUB-170125-7
- Date
- 2017
- Source
- Scientific Reports 7: 41280 (Journal)
- Registered Authors
- Gong, Zhiyuan, Li, Yanan, Spitsbergen, Jan
- Keywords
- Cancer genetics, Hepatocellular carcinoma
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cadherins/metabolism
- Carcinogenesis/metabolism
- Carcinogenesis/pathology
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/pathology*
- Cell Proliferation
- Disease Progression
- Doxycycline/pharmacology
- Doxycycline/therapeutic use
- Female
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology*
- Male
- Oncogenes
- Proto-Oncogene Proteins p21(ras)/genetics*
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- beta Catenin/metabolism
- PubMed
- 28117409 Full text @ Sci. Rep.
Citation
Li, Y., Li, H., Spitsbergen, J.M., Gong, Z. (2017) Males develop faster and more severe hepatocellular carcinoma than females in krasV12 transgenic zebrafish.. Scientific Reports. 7:41280.
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 krasV12 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/β-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 krasV12 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping