RRC ID 42921
Author Nobeyama Y, Okochi-Takada E, Furuta J, Miyagi Y, Kikuchi K, Yamamoto A, Nakanishi Y, Nakagawa H, Ushijima T.
Title Silencing of tissue factor pathway inhibitor-2 gene in malignant melanomas.
Journal Int J Cancer
Abstract To identify tumor-suppressor genes inactivated by aberrant methylation of promoter CpG islands (CGIs) in human malignant melanomas, genes upregulated by treatment of cells with a demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC), were searched for using oligonucleotide microarrays in melanoma cell lines, HMV-I, MeWo and WM-115. Seventy-nine known genes with CGIs were identified as being upregulated (>or=16-fold), and 18 of them had methylation of their putative promoter CGIs in 1 or more of 8 melanoma cell lines. Among the 18 genes, TFPI-2, which is involved in repression of the invasive potential of malignant melanomas, was further analyzed. Its expression was repressed in a melanoma cell line with its complete methylation, and was restored by 5-aza-dC treatment. It was unmethylated in cultured neonatal normal epidermal melanocyte, and was induced by ultraviolet B. In surgical melanoma specimens, TFPI-2 methylation was detected in 5 of 17 metastatic site specimens (29%), while it was not detected in 20 primary site specimens (0%) (p=0.009). By immunohistochemistry, the 5 specimens with promoter methylation lacked immunoreactivity for TFPI-2. The results showed that TFPI-2 is silenced in human malignant melanomas by methylation of its promoter CGI and suggested that its silencing is involved in melanoma metastasis.
Volume 121(2)
Pages 301-7
Published 2007-7-15
DOI 10.1002/ijc.22637
PMID 17372906
MeSH Azacitidine / analogs & derivatives Azacitidine / pharmacology Cell Line, Tumor Cells, Cultured CpG Islands DNA Methylation / drug effects Decitabine Gene Expression Regulation / radiation effects Gene Silencing* Glycoproteins / genetics* Glycoproteins / metabolism Humans Immunohistochemistry Melanoma / genetics* Melanoma / metabolism Melanoma / pathology Neoplasm Metastasis Oligonucleotide Array Sequence Analysis Promoter Regions, Genetic / genetics Reverse Transcriptase Polymerase Chain Reaction Ultraviolet Rays
IF 4.982
Times Cited 46
Human and Animal Cells