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
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
    Aoki, M
    Batista, O
    Bellacosa, A
    Tsichlis, P
    Vogt, PK
    [J]. 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
    Aoki, M
    Hecht, A
    Kruse, U
    Kemler, R
    Vogt, PK
    [J]. 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
    Barth, AIM
    Stewart, DB
    Nelson, WJ
    [J]. 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
    Bienz, M
    Clevers, H
    [J]. 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
    Eastman, Q
    Grosschedl, R
    [J]. 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
    Fu, SL
    Bottoli, I
    Goller, M
    Vogt, PK
    [J]. 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
    Guger, KA
    Gumbiner, BM
    [J]. DEVELOPMENTAL BIOLOGY, 2000, 223 (02) : 441 - 448
  • [9] Identification of c-MYC as a target of the APC pathway
    He, TC
    Sparks, AB
    Rago, C
    Hermeking, H
    Zawel, L
    da Costa, LT
    Morin, PJ
    Vogelstein, B
    Kinzler, KW
    [J]. SCIENCE, 1998, 281 (5382) : 1509 - 1512
  • [10] The p300/CBP acetyltransferases function as transcriptional coactivators of β-catenin in vertebrates
    Hecht, A
    Vleminckx, K
    Stemmler, MP
    van Roy, F
    Kemler, R
    [J]. EMBO JOURNAL, 2000, 19 (08) : 1839 - 1850