β-catenin is temporally regulated during normal liver development

被引:136
作者
Micsenyi, A [1 ]
Tan, XP [1 ]
Sneddon, T [1 ]
Luo, JH [1 ]
Michalopoulos, GK [1 ]
Monga, SPS [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Pittsburgh Canc Inst, McGowan Inst Regenerat Med,Dept Pathol, Pittsburgh, PA 15261 USA
关键词
D O I
10.1053/j.gastro.2003.12.047
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background Aims: beta-Catenin, a key component of the Wnt pathway, plays an important role in unregulated liver growth in liver tumors, in regulated growth during liver regeneration, and in ex vivo embryonic liver cultures. Methods: We used developing livers from several stages of gestational development to examine beta-catenin expression, protein-protein interactions, localization, and regulation in prenatal and postnatal livers. Results: Microarray, Northern, and protein analyses showed peak expression of beta-catenin during early liver development at Embryonic day 10 (E10)-E12, followed by a decrease and a complete loss of normal beta-catenin (97-kilodalton species) after E16 through the remaining prenatal period. At the early stages, beta-catenin localized to the cytoplasm and nuclei of resident cells in addition to its normal membranous localization, which was seen at all later stages and in adult liver. Decreases in beta-catenin levels at E14 onward coincided with its decreased gene expression and increased degradation, as seen by an increase in serine 45/threonine 41-phosphorylated beta-catenin and its other negative regulators, such as axin, adenomatous polyposis coli gene product (APC), and glycogen synthase kinase-3beta. Finally, we showed an intact association of E-cadherin and beta-catenin despite the loss of beta-catenin at E16-E18, owing to the presence of membrane-associated smaller-molecular-weight beta-catenin species. Conclusions: We also identified a stage-specific expression and regulation of beta-catenin during liver development that might be crucial for physiological liver development. Nuclear and cytoplasmic beta-catenin corresponded to cell proliferation in liver development. Finally, a smaller-molecular-weight species of beta-catenin might be maintaining normal interactions at the membrane.
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页码:1134 / 1146
页数:13
相关论文
共 40 条
[1]   beta-catenin is a target for the ubiquitin-proteasome pathway [J].
Aberle, H ;
Bauer, A ;
Stappert, J ;
Kispert, A ;
Kemler, R .
EMBO JOURNAL, 1997, 16 (13) :3797-3804
[2]   Epithelial mesenchymal interactions in cancer and development [J].
Arias, AM .
CELL, 2001, 105 (04) :425-431
[3]   Wnt signaling: a common theme in animal development [J].
Cadigan, KM ;
Nusse, R .
GENES & DEVELOPMENT, 1997, 11 (24) :3286-3305
[4]  
Cadoret A, 2001, CANCER RES, V61, P3245
[5]  
de La Coste A, 1998, P NATL ACAD SCI USA, V95, P8847
[6]   Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification [J].
Farr, GH ;
Ferkey, DM ;
Yost, C ;
Pierce, SB ;
Weaver, C ;
Kimelman, D .
JOURNAL OF CELL BIOLOGY, 2000, 148 (04) :691-701
[7]   Identification of c-MYC as a target of the APC pathway [J].
He, TC ;
Sparks, AB ;
Rago, C ;
Hermeking, H ;
Zawel, L ;
da Costa, LT ;
Morin, PJ ;
Vogelstein, B ;
Kinzler, KW .
SCIENCE, 1998, 281 (5382) :1509-1512
[8]   β-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection [J].
Huang, H ;
Fujii, H ;
Sankila, A ;
Mahler-Araujo, BM ;
Matsuda, M ;
Cathomas, G ;
Ohgaki, H .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (06) :1795-1801
[9]   Wnt signalling required for expansion of neural crest and CNS progenitors [J].
Ikeya, M ;
Lee, SMK ;
Johnson, JE ;
McMahon, AP ;
Takada, S .
NATURE, 1997, 389 (6654) :966-970
[10]   FROM CADHERINS TO CATENINS - CYTOPLASMIC PROTEIN INTERACTIONS AND REGULATION OF CELL-ADHESION [J].
KEMLER, R .
TRENDS IN GENETICS, 1993, 9 (09) :317-321