Molecular cloning of rat precursor cathepsin H and the expression of five lysosomal cathepsins in normal tissues and in a rat carcinosarcoma.

1. A rat cathepsin H cDNA was isolated from a rat liver cDNA library with synthetic oligonucleotide probes. 2. DNA sequence analysis indicated that it codes for rat preprocathepsin H. 3. Using this clone together with the cDNA for cathepsins B, D, L and S as probes, the expression of five major lysosomal proteinases was investigated in ten different normal rat tissues and in a rat carcinoma. 4. The common feature of their expression is that the five cathepsins have relatively high mRNA levels in lung and kidney, suggesting that they all play important roles in organs engaged in active protein metabolism. 5. In other tissues, the concentrations of the five cathepsin mRNAs are significantly different. This may indicate that their expressions are differentially regulated and that they may have specialized functions in specific tissues. 6. The cathepsin B mRNA level is at least 2.5-fold higher in the rat W256-carcinoma than in any of the normal rat tissues surveyed. 7. In contrast, the mRNA levels for the other four cathepsins show no comparable elevations. 8. This finding is consistent with previous observations reporting a correlation between cathepsins B expression and malignant tumors.