Open AccessEpigenetic inactivation of SFRP genes in oral squamous cell carcinoma
Author(s) -
Yohei Sogabe,
Hiromu Suzuki,
Minoru Toyota,
Kazuhiro Ogi,
Takashi Imai,
Masanori Nojima,
Yasushi Sasaki,
Hiroyoshi Hiratsuka,
Takashi Tokino
Publication year - 1992
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_32_6_1253
Subject(s) - wnt signaling pathway , biology , carcinogenesis , cancer research , epigenetics , ectopic expression , cdh1 , gene silencing , cell growth , dna methylation , cell , methylation , cancer , cell culture , signal transduction , microbiology and biotechnology , gene , cadherin , genetics , gene expression
Although mutations of APC, CTNNB1 (beta-catenin) and AXIN1 are rare in oral squamous cell carcinoma (OSCC), activation of the Wnt signaling pathway is thought to play an important role in oral carcinogenesis. In the present study, we examined the relationship between Wnt signaling and epigenetic alteration of the secreted frizzled-related protein (SFRP) genes in OSCC. We frequently detected loss of membrane localization of beta-catenin and its cytoplasmic or nuclear accumulation in OSCC cell lines, although these cell lines showed no APC or CTNNB1 (beta-catenin) mutations and no methylation of CDH1 (E-cadherin). By contrast, we frequently detected methylation of SFRP1 (7/17, 41%) SFRP2 (16/17, 94%) and SFRP5 (14/17, 82%) in a panel of OSCC cell lines, as well as in specimens of primary tumors collected from 44 OSCC patients (SFRP1, 10/42, 24%; SFRP2, 16/44, 36%; SFRP5, 7/43, 16%). We also observed that OSCC cell lines express various Wnt ligands, and that ectopic expression of SFRPs inhibited cancer cell proliferation. Our results confirm the frequent methylation and silencing of SFRP genes in OSCC, and suggest that their loss of function contributes to activation of Wnt signaling that leads to cell proliferation during oral carcinogenesis.