Speckle-type POZ protein acts as a predictive biomarker for mTOR target therapy in renal cell carcinoma

摘要

Renal cell carcinoma (RCC) develops resistance to most of the conventional therapies. In recent years inhibitors are being used to interfere with growth of cancer cells at molecular level and are found to be the most effective treatment option. However, some patients have to deal with severe side effects. Till date there have been no specific predictive biomarkers available to predict the target response and patient's stratification. We evaluate the expression of speckle-type POZ protein (SPOP) as a predictive biomarker in the presence of mTOR target therapy. Tissue samples were collected after nephrectomies from patients with RCC. Further primary culture was established from tissues of low-and high-grade RCC. Working concentration of inhibitors (CCI-779 and SB203580) was selected by MTT assay on A-498 cell line. Western blot was performed to study the p38MAPK, mTOR and SPOP protein expression. Primary culture showed more than 70% positivity for pan-cytokeratin. The concentration of 20 mu M of CCI-799 and 25 mu M SB203580 caused 30% and 20% cell death respectively. Expression of SPOP protein was decreased in CCI-779-treated cells. The combined treatment of CCI-779 and SB203580 had more inhibitory effects on SPOP in all cells types. However, SB203580 had no effect on SPOP expression. The results underline that, SPOP could be used as a potential predictive biomarker to assess the response of therapy with mTOR inhibitor (CCI-779).