Role of proteasome system in prognosis of breast cancer progression

The aim of this study was to compare the activity of proteasomes with different variants of tumor progression in luminal and triple-negative breast cancer (BC).

Materials and methods. 132 patients with primary luminal and triple-negative breast cancer in stage Т_1-3N0₂M₀ who had not received neoadjuvant treatment were included in this study. Proteasome chymotrypsin-like (ChTL) and caspase-like (CL) activities were determined by hydrolysis of fluorogenic peptides Suc-LLVY-AMC and Z-LLGlu-AMC in samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue.

Results: Results. The increased level of ChTL and CL proteasomal activity in the tumor were observed in comparison with adjacent tissues for all molecular subtypes of BC. The process of lymphogenic metastasis of luminal A and luminal B subtypes of breast cancer is associated with significant changes in the CL activity of the proteasome. Caspase-like activity of proteasomes was increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), and on the other hand it was decreased in the luminal B subtype of cancer. For the hematogenic pathway of breast cancer progression the ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role. The increase in proteasome activity in the tumor over the activity of proteasomes in adjacent tissues more than 2 times was associated with poor metastatic-free prognosis of the disease.

luminal breast cancer, triple negative breast cancer, lymphogenous metastasis, hematogenous metastasis, activity of proteasomes

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