Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/34723
Title: RAS AND RHO COREGULATE LIVER DEVELOPMENT AND HEPATOCELLULAR CARCINOMA IN ZEBRAFISH
Authors: CHEW TI WENG
Keywords: Kras, RhoA, zebrafish, hepatocellular carcinoma, crosstalk, GTPases
Issue Date: 10-Jan-2012
Source: CHEW TI WENG (2012-01-10). RAS AND RHO COREGULATE LIVER DEVELOPMENT AND HEPATOCELLULAR CARCINOMA IN ZEBRAFISH. ScholarBank@NUS Repository.
Abstract: RAS and Rho GTPases are key molecular switches that regulate many cellular processes. Much has been learnt about their individual functions but their signaling crosstalk in vivo remains largely unknown. Furthermore, their crosstalk in RAS-mediated transformation in vitro remains highly controversial. Inducible liver-specific Tet-on transgenic zebrafish expressing Kras G12V, RhoA, RhoA G14V or RhoA T19N, and double transgenic expressing Kras G12V with each of the three RhoA variants were created. During early development, Kras G12V caused liver enlargement concomitant with elevated Raf/MAPK and PI3K/AKT signaling. This liver enlargement was augmented by RhoA T19N co-expression, but reduced by RhoA G14V co-expression. Oncogenic Kras expression in adult fish caused the development of HCC with increased mortality, and inhibition of RhoA signaling (by RhoA T19N co-expression) further increased the death rate significantly. This study represents the first in vivo investigation of previously unappreciated signaling crosstalk between Ras and Rho in regulating hepatocyte transformation.
URI: http://scholarbank.nus.edu.sg/handle/10635/34723
Appears in Collections:Ph.D Theses (Open)

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