RRC ID 1220
著者 Takeuchi T, Liang SB, Matsuyoshi N, Zhou S, Miyachi Y, Sonobe H, Ohtsuki Y.
タイトル Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma.
ジャーナル Lab Invest
Abstract We previously reported that T-cadherin (CDH13, H-cadherin), a unique cadherin molecule, was expressed on the basal cell layer in normal murine and human epidermis. In the present study, T-cadherin expression in archival human skin specimens comprising a spectrum of human squamous cell neoplasia was investigated. T-cadherin expression was observed in both normal epidermal basal cells and adnexal epithelial cells of formalin-fixed and paraffin-embedded tissue sections. Western immunoblotting also revealed that mature T-cadherin protein was expressed in cultured human skin tissue equivalent. Atypical keratinocytes in 27 of 53 specimens of actinic keratosis and 23 of 30 specimens of Bowen's disease expressed T-cadherin. In contrast, T-cadherin was focally expressed in 6 of 56 invasive cutaneous squamous cell carcinomas. To explore the molecular mechanism of down-regulation of T-cadherin expression in invasive squamous cell carcinoma, loss of heterozygosity, genetic alternations, and methylation status in the 5' region of the T-cadherin gene were investigated. Loss of heterozygosity at intron 1 of the T-cadherin gene was observed in 8 of 28 informative cases of invasive squamous cell carcinoma. Although no structural genomic alternations were found by sequence analysis, aberrant promoter methylation of the T-cadherin gene was found in 12 of 28 invasive squamous cell carcinomas. T-cadherin expression was restored in cultured A431 cells, in which aberrant methylation was found by treatment with the demethylating agent 5'-aza-2-deoxycytidine. These findings suggest that a combination of deletion and aberrant methylation of the T-cadherin gene may play a role in loss of gene expression in a considerable number of invasive cutaneous squamous cell carcinomas.
巻・号 82(8)
ページ 1023-9
公開日 2002-8-1
DOI 10.1097/01.lab.0000025391.35798.f1
PMID 12177241
MeSH Cadherins / biosynthesis* Cadherins / genetics Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* DNA Methylation Down-Regulation Gene Deletion Humans Skin Neoplasms / genetics Skin Neoplasms / metabolism*
IF 4.197
引用数 56
WOS 分野 PATHOLOGY MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
ヒト・動物細胞 DJM-1(RCB0736) A431(RCB0202)