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Downregulation of expression of a novel cadherin molecule, T‐cadherin, in basal cell carcinoma of the skin
Author(s) -
Takeuchi Tamotsu,
Liang ShengBen,
Ohtsuki Yuji
Publication year - 2002
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10088
Subject(s) - biology , basal cell carcinoma , loss of heterozygosity , cadherin , downregulation and upregulation , dna methylation , methylation , cancer research , pathology , metastasis , tumor suppressor gene , cancer , cell , gene expression , gene , allele , carcinogenesis , genetics , basal cell , medicine
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. © 2002 Wiley‐Liss, Inc.