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Silencing of Wnt5a during colon cancer metastasis involves histone modifications of the gene
Author(s) -
Li Qian,
Chen Hong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.916.2
Subject(s) - trichostatin a , gene silencing , cancer research , colorectal cancer , metastasis , histone deacetylase , cancer , wnt signaling pathway , biology , dna methylation , histone , medicine , gene expression , signal transduction , gene , microbiology and biotechnology , genetics
Colon cancer is the third most common cancer in the United States. Approximately 90% of colon cancer deaths arise from the metastasis of primary tumors. Aberrant expression of Wnt5a, one of the WNT signaling factors, has been reported during colon cancer development and progression. This study tested the hypothesis that silencing of Wnt5a contributed to the colon cancer metastasis. We used the cell line models SW480 and SW620, which are poorly and highly metastatic colon cancer cell lines, respectively. SW480 was established from a primary human colon cancer, and SW620 was from a lymph node metastasis in the same patient. Wnt5a mRNA expression was more than 1,000 times lower in the metastatic SW620 than in SW480. Chromatin immunoprecipitation showed less association of RNA polymerase II with Wnt5a promoter region in SW620 compared to SW480, confirming the low transcriptional activity in SW620. There were much lower levels of acetylated histone H3 and H4 at the promoter region of Wnt5a. Although the demethylation reagent 5‐aza‐cytidine caused induction of Wnt5a expression, methylation of the promoter CpG island was not affected. Histone deacetylase inhibitors trichostatin A and sodium butyrate both significantly increased the mRNA expression of Wnt5a in SW620. In conclusion, our study suggested that the silencing of Wnt5a in highly invasive colon cancer might result from decreased histone acetylation.