Functional Smoothened is required for expression of GLI3 in colorectal carcinoma cells

被引:23
作者
Zhu, YH [1 ]
James, RM [1 ]
Peter, A [1 ]
Lomas, C [1 ]
Cheung, F [1 ]
Harrison, DJ [1 ]
Bader, SA [1 ]
机构
[1] Univ Edinburgh, Western Gen Hosp, Sir Alastair Currie Canc Res UK Labs, Div Pathol,Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland
关键词
hedgehog signalling; colon cancer; developmental genes; gene expression; methylation;
D O I
10.1016/j.canlet.2003.10.025
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated a role for Hedgehog signalling in colon cancer by studying transcription of members of the pathway in human colorectal carcinoma cell lines. We determined the methylation status and screened the gene encoding the Hedgehog receptor-associated protein Smoothened (SMO) for putative mutations. In three cell lines lacking SMO expression the SMO promoter was fully methylated and the transcription factor GLI3 was not expressed. Two additional cell lines both having one methylated SMO allele and expressing mutant SMO did not express GLI3. Our results suggest that expression of wild-type SMO is required for expression of GLI3 by a mechanism that is independent of conventional Hedgehog signalling. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:205 / 214
页数:10
相关论文
共 36 条
  • [31] Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb
    Wang, BL
    Fallon, JF
    Beachy, PA
    [J]. CELL, 2000, 100 (04) : 423 - 434
  • [32] Disruption of hedgehog signaling reveals a novel role in intestinal morphogenesis and intestinal-specific lipid metabolism in mice
    Wang, LC
    Nassir, F
    Liu, ZY
    Ling, L
    Kuo, F
    Crowell, T
    Olson, D
    Davidson, NO
    Burkly, LC
    [J]. GASTROENTEROLOGY, 2002, 122 (02) : 469 - 482
  • [33] Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer
    Watkins, DN
    Berman, DM
    Burkholder, SG
    Wang, BL
    Beachy, PA
    Baylin, SB
    [J]. NATURE, 2003, 422 (6929) : 313 - 317
  • [34] Progression of vertebrate limb development through SHH-mediated counteraction of GLI3
    Welscher, PT
    Zuniga, A
    Kuijper, S
    Drenth, T
    Goedemans, HJ
    Meijlink, F
    Zeller, R
    [J]. SCIENCE, 2002, 298 (5594) : 827 - 830
  • [35] Mechanisms of Wnt signaling in development
    Wodarz, A
    Nusse, R
    [J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 : 59 - 88
  • [36] Activating Smoothened mutations in sporadic basal-cell carcinoma
    Xie, JW
    Murone, M
    Luoh, SM
    Ryan, A
    Gu, QM
    Zhang, CH
    Bonifas, JM
    Lam, CW
    Hynes, M
    Goddard, A
    Rosenthal, A
    Epstein, EH
    de Sauvage, FJ
    [J]. NATURE, 1998, 391 (6662) : 90 - 92