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Isolation and Sequence Analysis of Human Cadherin-6 Complementary DNA for the Full Coding Sequence and Its Expression in Human Carcinoma Cells¹

Hirohashi Cell Configuration Project, ERATO, Research Development Corporation of Japan (JRDC), Tsukuba Research Consortium, 5-9-4 Tokodai, Tsukuba 300-26 [Y. S., S. H.]; Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104 [Y. S., M. G., T. T., S. H.]; and Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 [Y. S., M. K.], Japan

The expression pattern of E- and P-cadherin in human carcinomas has been reported by many laboratories. However, little is known about the involvement of other cadherin types in human carcinomas. cDNA clones for a cadherin molecule were isolated from a cDNA library of human hepatocellular carcinoma cells which lacked E- and P-cadherin expression but exhibited cell aggregation activity mediated by an unknown cadherin, and they were subjected to sequence analysis. The overlapped clones covered 4315 nucleotides and were found to encode a typical cadherin molecule consisting of 790 amino acids. Since the deduced amino acid sequence was identical to a partially available human cadherin-6 sequence except for two amino acid residues, the clones were considered to be human cadherin-6 cDNAs encoding the entire open reading frame. The deduced amino acid sequence also showed extremely high homology with recently reported rat K-cadherin, 97% for the putative mature protein, suggesting that cadherin-6 is the human counterpart of rat K-cadherin. Expression of cadherin-6 in various human normal tissues and carcinoma cells was examined by Northern blot analysis using a specific probe corresponding to the signal and precursor sequence. Among normal tissues examined, brain, cerebellum, and kidney showed strong expression of cadherin-6, whereas lung, pancreas, and gastric mucosa showed weak expression. Transcripts of cadherin-6 were not detected in normal liver, whereas four of six hepatocellular carcinoma cell lines examined expressed cadherin-6 abundantly. As reported for rat K-cadherin, three renal carcinoma cell lines also expressed cadherin-6 strongly. The most interesting finding was obtained for small cell lung carcinoma lines. Among 15 of such cell lines examined, all of 11 cadherin-6-positive lines were classified into the classic type, whereas the negative cell lines were all of the variant type. The present results suggest that besides E- and P-cadherin, other cadherin molecules are expressed in human cancers and are responsible for additional biological properties of the carcinoma cells.

¹ This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare of Japan for the 2nd Term: Comprehensive 10-Year Strategy for Cancer Control.

² To whom requests for reprints should be addressed.

Received 12/28/94. Accepted 3/15/95.

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