Open AccessDICKKOPF‐4 and ‐2 genes are upregulated in human colorectal cancer
Author(s) -
Matsui Akira,
Yamaguchi Tatsuya,
Maekawa Shinya,
Miyazaki Chikako,
Takano Shinichi,
Uetake Tomoyoshi,
Inoue Taisuke,
Otaka Masahiko,
Otsuka Hiroyuki,
Sato Tadashi,
Yamashita Atsuya,
Takahashi Yuka,
Enomoto Nobuyuki
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01272.x
Subject(s) - wnt signaling pathway , downregulation and upregulation , cancer research , colorectal cancer , beta catenin , biology , cancer , medicine , signal transduction , gene , microbiology and biotechnology , genetics
To comprehensively screen for genetic events underlying colorectal cancer, we performed suppression subtraction hybridization analysis on an advanced colon cancer. Because Dickkopf‐4, a member of the Dickkopf family acting as a Wnt‐signaling modulator, was identified as one of the upregulated genes in this specimen, we investigated expression profiles of all the Dickkopf family members in 55 colorectal tumors (21 cancers and 34 adenomas). We also investigated mechanisms regulating the expression of Dickkopf‐4 in these cancers in vitro and in vivo . Compared with normal adjacent mucosae, Dickkopf‐4 (median 27.4, P < 0.01) and ‐2 (median 51.4, P < 0.01) were strongly expressed in colorectal cancers. The level of Dickkopf‐4 was positively correlated with fibroblast growth factor‐20 (r s = 0.61, P = 0.00017), a representative β‐catenin transcriptional target gene, and with the degree of nuclear accumulation of β‐catenin in colorectal tumors. Dickkopf‐4 was induced by activated β‐catenin in vitro . Reciprocally, recombinant Dickkopf‐4 significantly inhibited T‐cell factor/lymphocyte enhancer factor reporter activity stimulated by recombinant Wnt3a in human embryonic kidney 293 cells. We conclude that Dickkopf‐4 and ‐2 are significantly upregulated in most colorectal tumors, and that Dickkopf‐4 upregulation reflects activation of the Wnt/canonical pathway. ( Cancer Sci 2009; 100: 1923–1930)