Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/30707
Title: Generation and Analysis of KRAS v12 in Driving Liver Tumorigenesis using transgenic zebrafish models
Authors: NGUYEN ANH TUAN
Keywords: Liver Cancer, Hepatocellular Carcinoma, Kras, Transgenic Zebrafish, Mifepristone-inducible, Cre/loxP
Issue Date: 25-Jul-2011
Source: NGUYEN ANH TUAN (2011-07-25). Generation and Analysis of KRAS v12 in Driving Liver Tumorigenesis using transgenic zebrafish models. ScholarBank@NUS Repository.
Abstract: Human liver cancer is one of the deadliest cancers worldwide, with hepatocellular carcinoma (HCC) being the most common type. Although aberrant Ras signaling has been implicated in the development and treatment of human HCC, a complete understanding of its molecular mechanisms in hepatocarcinogenesis remains elusive. In this study, a transgenic zebrafish HCC model was first generated by constitutively expressing oncogenic krasV12 to the liver. Fusing krasV12 to EGFP allows visualization of tumor development from early stages. Only a high level of krasV12 expression initiated liver tumorigenesis, which progressed from hyperplasia to invasive HCC with hyperactivation of the ERK and Wnt/?-catenin pathways, as well as by a loss of the p53-dependent senescence response. Microarrays analysis and cross-species comparisons further delineated several HCC gene signatures evolutionarily conserved between zebrafish and human liver cancer. However, this model exhibited low tumor occurrence and premature lethality due to early Ras activation. Therefore, two additional transgenic zebrafish liver tumor models utilizing the mifepristone-inducible and Cre/loxP strategies were established to spatio-temporally control krasV12 expression and to accelerate tumor onset. Adopting these inducible systems in which high incidence and consistent pattern of cancer progression coupled with low maintenance costs of zebrafish would allow systematic study of liver cancer progression and regression as well as provide useful platforms for genetic and anti-cancer drug screens.
URI: http://scholarbank.nus.edu.sg/handle/10635/30707
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
PhD Thesis - Nguyen Anh Tuan - HT070541Y.pdf8.85 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

315
checked on Dec 11, 2017

Download(s)

504
checked on Dec 11, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.