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Isolation of Complementary DNA Encoding K-Cadherin, a Novel Rat Cadherin Preferentially Expressed in Fetal Kidney and Kidney Carcinoma¹

First Department of Pathology [Y-Y. X., M. T., M. S., H. I., E. K., Y. N., H. S., I. K.] and Department of Urology [Y. O.], Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-31, Japan, and Department of Precancerous Studies, Henan Medical University, Zhengzhou, Henan 450052, People's Republic of China [Q. S.]

Complementary DNA for a novel member of the cadherin family, designated K-cadherin, was isolated from a rat renal cell carcinoma complementary DNA library by screening it with a short complementary DNA probe which was initially obtained from the RNA of day 16 fetal Wistar rat stomach mucosa by the polymerase chain reaction. The deduced primary structure of K-cadherin is 789 amino acid residues, which contain five internal repeats in its extracellular domain, a single putative transmembrane domain, and a cytoplasmic tail characteristic of those of classic type cadherins. K-cadherin exhibits low homology with mature proteins of mouse N- (38%), E- (35%), and P-cadherin (32%), and high homology with a partially identified human cadherin-6 protein (95%) at the amino acid level. Northern blot analysis revealed a high level of expression of K-cadherin mRNA in fetal rat kidney and brain, and rat kidney carcinoma with two major transcripts, 4.1 and 8.0 kilobases in size, whereas there was very weak or no expression in any organ of adult rats. The level of K-cadherin expression was also elevated in some human kidney cancer tissues. In the developing kidney, in situ hybridization showed localization of K-cadherin mRNA in the nephroblastic epithelial cells of comma bodies coinciding with those in the process of polarization during glomeruloneogenesis. These results demonstrate that K-cadherin must have important functions in both the process of kidney development and tumorigenesis of some types of kidney cancer.

¹ This work is supported in part by the Smoking Research Foundation, the Ministry of Education, Culture and Science of Japan (05151015, 05151023, 05151025), and the Ministry of Health and Welfare of Japan.

² Recipient of a fellowship from the Japan Society for Promotion of Science for Junior Scientists.

³ To whom requests for reprints should be addressed.

Received 12/22/93. Accepted 3/29/94.

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