Proteases are enzymes which are significantly involved in many cellular processes. Proteases influence activity of many other proteins, so their adequate regulation is very important. Cysteine cathepsins are primarily found in lysosomes and require a reducing environment to function. The main inhibitors of cysteine cathepsins are cystatins, among which the key inhibitors are cystatin C and stefin B. Cystatins regulate excessive cysteine cathepsins activity. Both have a significant impact on the pathogenesis of cancer and other diseases. The role of cystatins, however, is not just to inhibit cysteine cathepsins activity. Several studies have suggested a significant effect of cystatins on other cellular pathways including proliferation and differentiation.
Breast cancer is the most common cancer among women worldwide. The mouse has emerged as an important animal model for human breast cancer because the mammary glands of the two species are very similar. So research studies of human breast cancer are conducted on various transgenic mouse models of breast adenocarcinoma, such as MMTV-PyMT.
In the master’s thesis we studied the effect of cystatin C and stefin B on the presence of macrophages in the MMTV-PyMT mouse mammary cancer model and in the transgenic MMTV-PyMT mouse mammary cancer models with knocked out genes for cystatin C and stefin B. We wanted to evaluate their impact on cancer progression. Tumour slices were stained with primary F4-80 antibodies and the DAB substrate system. We have found out that the lowest number of macrophages was present in transgenic mice with knocked out genes for both cystatins. We have concluded that both significantly contribute to cancer progression, but their exact role in the processes has not yet been defined.
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