Abstract
Introduction.The efficacy of anticancer treatment depends on biological factors of tumor.The aimof the study was to determine the activity of proteasomes and calpains and to reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues.Methods.Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEGF were measured using ELISA kits. The levels of proteasome subunits were measured by Western Blotting. Proteasome and calpain activities were determined using specific fluorogenic substrates.Results.We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in transcription and growth factor levels in primary kidney cancer tissues. The proteolysis activation was found in metastatic tissues.Conclusions.Our results suggest that NF-κΒ, HIF-1α and VEGF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.
Highlights
The efficacy of anticancer treatment depends on biological factors of tumor
Our results suggest that NF-κΒ, HIF-1α and vascular endothelial growth factor (VEGF) transcription factors and intracellular proteolytic systems are involved in kidney cancer progression
High expression levels of NF-κΒ, HIF-1α and VEGF were found in renal cell carcinoma (RCC) tissues
Summary
The aim of the study was to determine the activity of proteasomes and calpains and to reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues. Proteolysis is one of the mechanisms for regulation of NF-κΒ and HIF-1α transcription factors, and the proteasome and calpain systems are the most possible factors to be involved. A decrease in HIF-1α degradation in the presence of proteasome inhibitors or under hypoxia leads to a significant increase in both VEGF and its mRNA expression in tumor cells [26, 27]. The key moment of NF-κΒ activation belongs to breaking the ties between the transcription factor and repressor protein known as I-κB [8, 11]. The additional mechanism in NF-κΒ regulation serves the NF-κΒ protein forming from precursors, which are mediated by proteasomes through the modification of р105 protein [29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
