618 A Novel Somatic Mutation of β2sp Inactivates the TGF-β Pathway and Promotes Alcohol Induced HCC

Abstract

A S L D A b st ra ct s vehicle:1337±552 vs crecont, FGF-19:196±50 and c-foshypo, vehicle: 1395±315 vs c-foshypo, FGF-19:125±8]. ASBT protein levels were not reduced in the ileum of the c-fosintmice treated with FGF-19 [c-fosint-, vehicle: 1413±83 vs c-fosint-, FGF19: 1453±79]. FGF-19 treatment led to a marked increase in phospho-ERK1/2, JNK1 and JNK2 in both wild type and c-fosintmice [1) pERK1/2: wt: 2199±771 vs FGF-19: 8517±1170, c-fosint-,vehicle: 2963±1200 vs c-fosint-,FGF19: 9215±2200; 2) JNK1: wt: 268±130 vs FGF-19: 1433±249, c-fosint-,vehicle: 251±75 vs c-fosint-,FGF19: 1526±202; 3) JNK2: wt: 261±46 vs FGF-19: 897±152, c-fosint-,vehicle: 201±55 vs c-fosint-,FGF19: 1440±257]. p-c-jun was markedly increased in ileal nuclear extracts from wild type and c-fosintmice treated with FGF-19 [wt: 71±7 vs FGF-19: 1119±218; c-fos-/-,vehicle: 80±11 vs c-fos-/-,FGF19: 1179±245]. Nuclear pc-fos was increased in wild type mice but not in the c-fosintmice where c-fos was not expressed [wt: 1564±352 vs FGF-19: 7862±2635]. ASBT expression was repressed in the gallbladder in response to FGF-19 treatment of all mice including the c-fosintmice. Conclusion: Activation and phosphorylation of c-fos is critical to FGF-19 mediated repression of ASBT.