Downregulation of expression of a novel cadherin molecule, T-cadherin, in basal cell carcinoma of the skin.

Abstract

T-cadherin appears to act as a tumor-suppressor factor in various cancers. Downregulation of T-cadherin is caused by a combination of allelic loss and hypermethylation of the T-cadherin promoter region and is related to cancer invasion. To elucidate the molecular mechanism of invasiveness of basal cell carcinoma of the skin, T-cadherin expression was investigated in archival pathological tissue sections made up of normal counterparts of skin and various types of basal cell carcinoma. Immunohistochemical staining showed that T-cadherin was not expressed in 38 of 51 (75%) basal cell carcinoma specimens, whereas normal counterparts of the skin appeared to express abundant T-cadherin. Loss of heterozygosity in intron 1 of the T-cadherin gene was found in four of 20 informative cases that did not express T-cadherin. Aberrant methylation of the T-cadherin promoter region also was found in six of 25 basal cell carcinomas by methylation-specific polymerase chain reaction. In contrast, no structural alternations were found in two loss of heterozygosity-positive basal cell carcinomas on sequence analysis. These findings indicated that T-cadherin expression was downregulated by a combination of allelic loss and aberrant methylation in basal cell carcinoma of the skin. Loss of T-cadherin expression might be related to the biological behavior of basal cell carcinoma. In addition, results of the present study suggested that downregulation of T-cadherin in various cancers might be related to tumor invasiveness rather than metastasis, because basal cell carcinoma of the skin principally lacks metastatic activity.

• Authors: Tamotsu Takeuchi, Sheng-Ben Liang, Yuji Ohtsuki
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 35 Issue 4 Pg. 173-9 (Dec 2002) ISSN: 0899-1987 [Print] United States
• PMID: 12489108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• Cadherins
• DNA Primers
• H-cadherin

Topics

• Amino Acid Sequence
• Base Sequence
• Cadherins (genetics)
• Carcinoma, Basal Cell (genetics, pathology)
• DNA Primers
• Down-Regulation
• Humans
• Immunohistochemistry
• Loss of Heterozygosity
• Molecular Sequence Data
• Neoplasm Invasiveness
• Skin Neoplasms (genetics, pathology)