The role of proteases in development of cancer in mice

Abstract

Mice of the A/J strain are useful models for cancer because they develop tumours spontaneously after treatment with ethylcarbamate. The first study was to investigate the changes in protease activity in tumour bearing and in normal tissues such as lung, liver and skelatal muscle. Using a modified fluorescent assay, differences in m-calpain and calpastatin activity were found between seven and nine month ethyl carbamate treated mice. The calpain to calpastatin ratio is higher in the nine month treated mice due to a decline in the activity of calpastatin with age. Changes in the calpain activity may account for the rapid attenuation of protein degradation in tissues and the accumulation of muscle protein during the growth phase of mice. This study confirms the presence of m-calpain and calpastatin in normal and tumour tissues in mice. High activities of cathepsin B and B+L were found in tumour bearing tissues probably due to increased transcription of the cathepsin gene or stability of cathepsin B mRNA. Some malignant tissues secrete cathepsins which are thought to degrade the extracellular matrix. Cathepsins are, therefore, often involved in the invasion of cells by malignant cancer cells. The increased cathepsin B and B+L activities in this study confirm the involvement of cathepsins in tumour bearing tissues. Using mRNA differential display techniques, a number of different differentially expressed genes were identified in the tumour bearing and normal tissues. Further cloning and sequencing of these genes need to be carried out in the future.