Downregulation of expression of a novel cadherin molecule, T-cadherin, in basal cell carcinoma of the skin.
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.
Takeuchi
Tamotsu
T
Department of Pathology, Kochi Medical School, Japan.
Liang
Sheng-Ben
SB
Ohtsuki
Yuji
Y
D000595:Amino Acid Sequence; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D015820:Cadherins; D017931:DNA Primers; C099972:H-cadherin