ISOLATION OF COMPLEMENTARY-DNA ENCODING K-CADHERIN, A NOVEL RAT CADHERIN PREFERENTIALLY EXPRESSED IN FETAL KIDNEY AND KIDNEY CARCINOMA

Complementary DNA for a novel member of the cadherin family, designate d K-cadherin, was isolated from a rat renal cell carcinoma complementa ry DNA library by screening it with a short complementary DNA probe wh ich was initially obtained from the RNA of day 16 fetal Wistar rat sto mach mucosa by the polymerase chain reaction. The deduced primary stru cture of K-cadherin is 789 amino acid residues, which contain five int ernal repeats in its extracellular domain, a single putative transmemb rane 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 amin o acid level. Northern blot analysis revealed a high level of expressi on of K-cadherin mRNA in fetal rat kidney and brain, and rat kidney ca rcinoma with two major transcripts, 4.1 and 8.0 kilobases in size, whe reas 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 kid ney cancer tissues. In the developing kidney, in situ hybridization sh owed localization of K-cadherin mRNA in the nephroblastic epithelial c ells of comma bodies coinciding with those in the process of polarizat ion during glomeruloneogenesis. These results demonstrate that K-cadhe rin must have important functions in both the process of kidney develo pment and tumorigenesis of some types of kidney cancer.