title: Males develop faster and more severe hepatocellular carcinoma than females in krasV12transgenic zebrafish.
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 krasV12transgenic 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 krasV12transgenic 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.
authors.affiliation: Department of Biological Sciences, National University of Singapore, 117543, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, National University of Singapore, 117543, Singapore.
authors.forename: Hankun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Microbiology, Oregon State University, Corvallis, Oregon, 97331, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Spitsbergen
authors.affiliation: Department of Biological Sciences, National University of Singapore, 117543, Singapore.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D009857:Oncogenes; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D029961:Zebrafish Proteins; D051176:beta Catenin; C000589775:Kras protein, zebrafish; D016283:Proto-Oncogene Proteins p21(ras); D004318:Doxycycline