Insulin-like growth factors (IGFs) and the nuclear factor κB (NF-κB) are known to play an important role in pathogenesis of endometrial cancer. However, there is still uncertainty about their proteolytic regulation. We studied the correlation between chymotrypsin-like activity of proteasomes and IGF-I, IGF-II, and NF-κB levels in endometrial cancer tissues. The total activity of proteasomes and the 20S and 26S proteasome activities were shown to be significantly higher in malignant tumors than in the unaltered endometrium. Negative correlations were found between the proteasome activity of 26S and the p50 level of NF-κB, as well as between the 26S and 20S proteasome activities and IGF-I level. The obtained data indicate the possible proteasome regulation of growth and transcription factors. As the major pool of IGF-I is considered to be located in the extracellular space, it is likely that extracellular proteasomes also take part in the regulation of the IGF-I content. The positive correlation between the IGF-I level and PAPP-A metalloproteinase is evidence that this proteolytic enzyme is another important regulator of the level of growth factor, which ensures the proteolysis of IGF-I binding proteins and, thus, increases the concentration of IGF-I in tissues. The present data show the possibility of the proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.