Dickkopf-1, an inhibitor of the Wnt signaling pathway, is induced by p53

Jian Wang, Jiang Shou, Xinbin Chen

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Dickkopf-1 (Dkk-1), a secreted glycoprotein, has been found to be necessary and sufficient for inducing amphibian head formation. Interestingly, the mechanism by which Dkk-1 does this is the ability of Dkk-1 to antagonize the Wnt signaling pathway. Wnt, itself a proto-oncoprotein, ran promote cell proliferation and transformation when mutated or overexpressed, leading to tumor formation. p53 is a tumor suppressor and loss of p53 function accelerates mammary tumorigenesis by Wnt. In this study, we found that Dkk-1 is induced by wild-type p53 but not mutant p53(R249S). In addition, DNA damage upregulates Dkk-1 in cell lines that harbor an endogenous wild-type p53 gene but not in cell lines that are p53-null or harbor an endogenous mutant p53 gene. We also found a potential p53 responsive element located approximately 2100 nucleotides upstream of the Dkk-1 transcription start site and we show that p53 binds specifically to this element both in vitro and in vivo. Furthermore, we have established several cell lines derived from H1299 lung carcinoma and U118 glioma cells that inducibly express Dkk-1 under a tetracycline-regulated promoter. We found that Dkk-1 has no effect on proliferation of cells that are not transformed by Wnt. Taken together, these results suggest that Dkk-1 may mediate p53 tumor suppression by antagonizing the Wnt signaling pathway.

Original languageEnglish (US)
Pages (from-to)1843-1848
Number of pages6
JournalOncogene
Volume19
Issue number14
StatePublished - Mar 30 2000
Externally publishedYes

Fingerprint

Wnt Signaling Pathway
p53 Genes
Cell Line
Cell Proliferation
Neoplasms
Transcription Initiation Site
Oncogene Proteins
Amphibians
Tetracycline
Glioma
DNA Damage
Glycoproteins
Carcinogenesis
Breast
Up-Regulation
Nucleotides
Head
Carcinoma
Lung

Keywords

  • Dickkopf-1
  • p53
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Dickkopf-1, an inhibitor of the Wnt signaling pathway, is induced by p53. / Wang, Jian; Shou, Jiang; Chen, Xinbin.

In: Oncogene, Vol. 19, No. 14, 30.03.2000, p. 1843-1848.

Research output: Contribution to journalArticle

Wang, J, Shou, J & Chen, X 2000, 'Dickkopf-1, an inhibitor of the Wnt signaling pathway, is induced by p53', Oncogene, vol. 19, no. 14, pp. 1843-1848.
Wang, Jian ; Shou, Jiang ; Chen, Xinbin. / Dickkopf-1, an inhibitor of the Wnt signaling pathway, is induced by p53. In: Oncogene. 2000 ; Vol. 19, No. 14. pp. 1843-1848.
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