International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

---

POSTER 132 - SEX HORMONE RESPONSIBLE FOR GENERATION OF HEPATOCELLULAR CARCINOMA IN TRANSGENIC MICE EXPRESSING M-H-RAS

Yu DY
KRIBB

Co-Authors: 1) Wang A G, 2) Moon H B, 1) Lee D S
Institutions: 1) KRIBB, 2) University of Wonkwang

Hepatocellular carcinoma (HCC) is predominant in the male gender. However, the molecular mechanism has not been studied. Model mice generating hepatocellular carcinoma by the expression of mutant H-Ras using albumin enhancer/promoter were produced. Grossly defined HCC was remarkably observed in male mice more than female mice by showing the incidence, 100% in the male, whereas 40% in the female at the age of 8 mon. The mice were orchiectomized or oophorectomized to know whether sex hormone might affect hepatic tumor generation. The incidence of HCC in the male orchiectomized at the age of 1 mon and sampled at the age of 6 mon was greatly decreased from 81.8% to 20%. However the female oophorectomized showed increased incidence of HCC compared to control from 0% to 25%. The incidence of HCC in the mice was paralleled to the expression level of transgene, mutant H-Ras by Real Time PCR. The expression level of mH-ras in the liver of orchiectomized transgenic mice was decreased to the level of female transgenic mice. It was remarkably increased in the oophorectomized mice. Raf/MEK/ERK kinase cascade was highly activated in male transgenic mice, but poorly or not in female transgenic mice and orchiectomized transgenic mice. These results suggest that sex hormone may regulate transcription of mH-Ras gene and affect the incidence of HCC by the subsequent activation of Raf/MEK/ERK.