Protelytic regulation of growth factors and HIF-1 in endometrial cancer

We studied the correlation between chymotrypsin-like activity of proteasomes and IGF-I, IGF-II, PAPP-A, VEGF, HIF-1 levels in endometrial cancer tissues. The total activity of proteasomes and the activity of the 20S and 26S proteasomes were shown to be significantly higher in the malignant tumors than in the normal endometrium. The relationships between the proteasome pool activity and IFG-I and HIF-1 expressions were found. The data obtained indicate the possible proteasome regulation of growth and transcription factors. The major pool of IGF-I is located in the extracellular space, and it is likely that extracellular proteasomes also take part in the regulation of the IGF-I content. The positive correlation between the IGF-I, HIF-1, VEGF levels and PAPP-A metalloproteinase give evidence that this proteolytic enzyme is one more important regulator of growth and transcription factors. The present data show the evidence of proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.