Oncogenic transformation by β-catenin:: deletion analysis and characterization of selected target genes

被引：28
作者：
Aoki, M [1 ]
Sobek, V
Maslyar, DJ
Hecht, A
Vogt, PK
机构：
[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
[2] Univ Freiburg, Inst Mol Med & Zellforsch, Freiburg, Germany
来源：
ONCOGENE | 2002年 / 21卷 / 46期
关键词：
beta-catenin; LEF/TCF; target genes; oncogenic transformation;
D O I：
10.1038/sj.onc.1205796
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Genetic analysis of beta-catenin-induced oncogenic transformation in chicken embryo fibroblasts (CEF) revealed the following prerequisites for oncogenicity: (1) removal of the N terminal phosphorylation sites targeted by glycogen synthase kinase 3beta (GSK3beta), (2) retention of the N terminal transactivation domain, and (3) retention of the armadillo repeats. The C terminal transactivation domain played an ancillary role in the transformation of CEF. There was a rough correlation between the transforming activity of various beta-catenin constructs and their transactivation of the TOPFLASH reporter. Expression levels of the candidate target genes of beta-catenin-LEF, cyclin D1 and myc were not correlated with each other or with the transforming activity of beta-catenin constructs. A new target gene, coding for inositol hexakisphosphate kinase 2 (IP6K2) was identified. Its expression showed concordance with the transforming activity of beta-catenin constructs.
引用
收藏
页码：6983 / 6991
页数：9
相关论文
共 44 条
[1]   The Akt kinase:: Molecular determinants of oncogenicity [J].
Aoki, M ;
Batista, O ;
Bellacosa, A ;
Tsichlis, P ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14950-14955
[2]   Nuclear endpoint of Wnt signaling: Neoplastic transformation induced by transactivating lymphoid-enhancing factor 1 [J].
Aoki, M ;
Hecht, A ;
Kruse, U ;
Kemler, R ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (01) :139-144
[3]   T cell factor-activated transcription is not sufficient to induce anchorage-independent growth of epithelial cells expressing mutant β-catenin [J].
Barth, AIM ;
Stewart, DB ;
Nelson, WJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) :4947-4952
[4]   Linking colorectal cancer to Wnt signaling [J].
Bienz, M ;
Clevers, H .
CELL, 2000, 103 (02) :311-320
[5]  
Dahmen RP, 2001, CANCER RES, V61, P7039
[6]   Regulation of LEF-1/TCF transcription factors by Wnt and other signals [J].
Eastman, Q ;
Grosschedl, R .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (02) :233-240
[7]   Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation [J].
Fu, SL ;
Bottoli, I ;
Goller, M ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) :5716-5721
[8]   A mode of regulation of β-catenin signaling activity in Xenopus embryos independent of its levels [J].
Guger, KA ;
Gumbiner, BM .
DEVELOPMENTAL BIOLOGY, 2000, 223 (02) :441-448
[9]   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
[10]   The p300/CBP acetyltransferases function as transcriptional coactivators of β-catenin in vertebrates [J].
Hecht, A ;
Vleminckx, K ;
Stemmler, MP ;
van Roy, F ;
Kemler, R .
EMBO JOURNAL, 2000, 19 (08) :1839-1850
12345