Loss of T-Cadherin (CDH13, H-Cadherin) Expression in Cutaneous Squamous Cell Carcinoma

Abstract

SUMMARY: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 5Ј 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 5Ј-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. (Lab Invest 2002, 82:1023-1029.

A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion

“…For the MSP assay, genomic DNA was obtained from paraffin tissue sections that contained both cancerous and noncancerous areas with the Pinpoint Slide DNA Isolation System as described previously (Takeuchi et al, 2002). Notably, we selected areas in which the tumor dose was at least over 50%.…”

“…Notably, we selected areas in which the tumor dose was at least over 50%. Genomic DNA was modified with sodium bisulfite according to the modified methods of Herman et al (1996) and Fan et al (2002) as previously described (Takeuchi et al 2002). Briefly, genomic DNA was suspended in 45 ml of 10 mM Tris-HCl (pH 7.4)/0.1 mM ethylenediaminetetraacetic acid with 5 ml 2N NaOH at 371C for 15 min.…”

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

“…2 Recent studies have highlighted the role of CDH13 as a TSG in lung, breast, ovarian, bladder, colorectal, esophageal, gastric, cutaneous, and pancreatic cancers. [3][4][5][6][7][8][9][10] Furthermore, downregulation of H-cadherin due to hypermethylation in the promoter region of CDH13 gene appears to be related to the tumorigenesis and invasiveness of these cancers. However, expression of H-cadherin and the methylation status of the CDH13 in pituitary tissue and pituitary adenomas have not been evaluated to date.…”

Genetic and epigenetic inactivation of T‐cadherin in human hepatocellular carcinoma cells

“…This is in accordance with the findings of hypermethylation of T-cadherin promoter in other human cancers. [31][32][33][34][35] More importantly, histone deacetylation, which has not been reported before, was also frequently observed in the hepatoma cell lines with relatively low Tcadherin expression levels. In addition, chromosome 16q24.2-24.3 is one of the frequent regions of allelic losses in human HCC.…”