Breast cancer is one of four oncology diseases that are most widespread in the world. Moreover, breast cancer is one of leading causes of cancer-related deaths in female population within economically developed regions of the world. So far, detection of new mechanisms of breast cancer development is very important for discovery of novel areas in which therapy approaches may be elaborated. The objective of the present study is to investigate involvement of proteasomes, which cleave up to 90% of cellular proteins and regulate numerous cellular processes, in mechanisms of breast cancer development. Proteasome characteristics in 106 patient breast carcinomas and adjacent tissues, as well as relationships of detected proteasome parameters with clinical-pathological factors, were investigated. Proteasome chymotrypsin-like activity was evaluated by hydrolysis of fluorogenic peptide Suc-LLVY-AMC. The expression of proteasome subunits was studied by Western-blotting and immunohistochemistry. The wide range of chymotrypsin-like activity in tumors was detected. Activity in tumors was higher if compared to adjacent tissues in 76 from 106 patients. Multiple analysis of generalized linear models discovered that in estrogen α-receptor absence, tumor growth was connected with the enhanced expression of proteasome immune subunit LMP2 and proteasome activator PA700 in tumor (at 95% confidence interval). Besides, by this analysis we detected some phenomena in adjacent tissue, which are important for tumor growth and progression of lymph node metastasis in estrogen α-receptor absence. These phenomena are related to the enhanced expression of activator PA700 and immune subunit LMP7. Thus, breast cancer development is connected with functioning of immune proteasome forms and activator PA700 in patients without estrogen α-receptors in tumor cells. These results could indicate a field for search of new therapy approaches for this category of patients, which has the worst prognosis of health recovery.

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Taken together, our results suggest that above mentioned transcription factors and intracellular proteolytic systems are involved in SCCHN progression and metastasis. Moreover, the opportunity of transcription factors regulation by proteasome takes place in oncogenesis of SCCHN. The results provide a basis for new prognostic tests and development of novel targeted therapy.

The ability to active movement in extracellular matrix wherein significant role plays remodeling of the cytoskeleton by actin-binding proteins may influence on the metastatic potential of tumor cells. We studied the expression of actin-binding proteins and β-catenin in connection with proteasome and calpain functioning in the tissues of primary tumors and metastases of ovarian cancer. The chymotrypsin-like proteasome activity and calpain activity were shown to be significantly higher in ovarian cancer than in normal tissues. Furthermore, the activity of the proteasome and calpain were significantly higher in the peritoneal metastases in comparison with primary tumors. Correlation analysis showed in the primary tumor tissue the presence of a positive relationship between the activity of calpain and chymotrypsin-like proteasome activity (r = 0.82; p = 0.0005), whereas in metastases this connection was not revealed. Contents of p45 Ser β-catenin and the actin-severing protein gelzolin were decreased in metastases relative to primary tumors. Level of cofilin, functionally similar to gelzolin protein, was significantly higher in metastases compared to primary ovarian tumor tissue. In ovarian cancer significant reduction in the number of the monomer binder protein thymosin-β4 was observed in primary tumors and metastases as compared to normal tissues, but significant differences between the primary tumor and metastases were not observed. In the tissues of primary tumors negative correlations were observed between the chymotrypsin-like activity of the proteasome and the amount of p45 Ser β-catenin and protein Arp3, a member of the Arp2/3 complex. In metastasis negative correlation were revealed between the activity of calpain and content Arp3, cofilin, thymosin. The data obtained suggest the existence of different mechanisms of proteolytic regulation of locomotor proteins in primary tumors and metastases in ovarian cancer.

We compared the content of adenylyl cyclase-associated protein 1 (CAP1) in the blood and tissues of patients with head and neck squamous cell carcinomas (with and without regional metastases), patients with chronic inflammatory diseases aggravated by laryngeal and laryngopharyngeal dysplasia, and healthy individuals. The data suggest that serum CAP1 concentration correlated with the depth of primary tumor invasion and the presence of regional metastases. In cancer patients, the serum level of CAP1 was lower than in patients with laryngeal and laryngopharyngeal dysplasia, which can be of importance for differential and timely diagnostics of malignant tumors.