Wnt inhibitory factor-1, a Wnt antagonist, is silenced by promoter hypermethylation in malignant pleural mesothelioma

被引:60
作者
Batra, S
Shi, Y
Kuchenbecker, KM
He, B
Reguart, N
Mikami, I
You, L
Xu, ZD
Lin, YC
Clément, G
Jablons, DM [1 ]
机构
[1] Univ Calif San Francisco, Ctr Comprehens Canc, Dept Surg, Thorac Oncol Lab, San Francisco, CA 94143 USA
[2] Hosp Badalona Germans Trias & Pujol, Med Oncol Serv, Inst Catala Oncol, Barcelona, Spain
关键词
Wnt inhibitory factor-1; Wnt signaling; promoter hypermethylation;
D O I
10.1016/j.bbrc.2006.02.084
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
Wilt inhibitory factor-1 (WIF-1) is a secreted protein that antagonizes Wilt signaling. We recently demonstrated the importance of aberrant activation of the Wilt signaling pathway in various cancers including malignant pleural mesothelioma. In this study, we revealed downregulated WIF-1 expression in cell lines and primary tissue when compared to normal mesothelial cell lines and adjacent pleura, respectively. We observed hypemethylation in four of four mesothelioma cell lines, but not in two normal mesothelial cell lines. In primary tissue samples, we observed methylation in three paired tumor specimens compared to their adjacent normal pleura and methylation in eight of nine unpaired tumor tissue samples. Taken together, our studies suggest that WIF-1 silencing due to its promoter hypermethylation is all important mechanism underlying the constitutively activated Wilt signaling in mesothelioma. New therapies toward inhibition of the Wilt pathway through WIF-1 might be promising for the future treatment of malignant mesothelioma. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1228 / 1232
页数:5
相关论文
共 48 条
[1]   Axin-mediated CKI phosphorylation of β-catenin at Ser 45:: a molecular switch for the Wnt pathway [J].
Amit, S ;
Hatzubai, A ;
Birman, Y ;
Andersen, JS ;
Ben-Shushan, E ;
Mann, M ;
Ben-Neriah, Y ;
Alkalay, I .
GENES & DEVELOPMENT, 2002, 16 (09) :1066-1076
[2]   The Wnt connection to tumorigenesis [J].
Behrens, J ;
Lustig, B .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2004, 48 (5-6) :477-487
[3]   Functional interaction of beta-catenin with the transcription factor LEF-1 [J].
Behrens, J ;
vonKries, JP ;
Kuhl, M ;
Bruhn, L ;
Wedlich, D ;
Grosschedl, R ;
Birchmeier, W .
NATURE, 1996, 382 (6592) :638-642
[4]   Mesothelioma clinical presentation [J].
Bueno, R .
CHEST, 1999, 116 (06) :444S-445S
[5]   The Wnt antagonist sFRP1 in colorectal tumorigenesis [J].
Caldwell, GM ;
Jones, C ;
Gensberg, K ;
Jan, S ;
Hardy, RG ;
Byrd, P ;
Chughtai, S ;
Wallis, Y ;
Matthews, GM ;
Morton, DG .
CANCER RESEARCH, 2004, 64 (03) :883-888
[6]   Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling [J].
Fedi, P ;
Bafico, A ;
Soria, AN ;
Burgess, WH ;
Miki, T ;
Bottaro, DP ;
Kraus, MH ;
Aaronson, SA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (27) :19465-19472
[7]   The gene expression signatures of melanoma progression [J].
Haqq, C ;
Nosrati, M ;
Sudilovsky, D ;
Crothers, J ;
Khodabakhsh, D ;
Pulliam, BL ;
Federman, S ;
Miller, JR ;
Allen, RE ;
Singer, MI ;
Leong, SPL ;
Ljung, BM ;
Sagebiel, RW ;
Kashani-Sabet, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (17) :6092-6097
[8]   The F-box protein β-TrCP associates with phosphorylated β-catenin and regulates its activity in the cell [J].
Hart, M ;
Concordet, JP ;
Lassot, I ;
Albert, I ;
del los Santos, R ;
Durand, H ;
Perret, C ;
Rubinfeld, B ;
Margottin, F ;
Benarous, R ;
Polakis, P .
CURRENT BIOLOGY, 1999, 9 (04) :207-210
[9]   A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells [J].
He, B ;
You, L ;
Uematsu, K ;
Xu, ZD ;
Lee, AY ;
Matsangou, M ;
McCormick, F ;
Jablons, DM .
NEOPLASIA, 2004, 6 (01) :7-14
[10]   Factors predictive of survival among 337 patients with mesothelioma treated between 1984 and 1994 by the Cancer and Leukemia Group B [J].
Herndon, JE ;
Green, MR ;
Chahinian, AP ;
Corson, JM ;
Suzuki, Y ;
Vogelzang, NJ .
CHEST, 1998, 113 (03) :723-731