The expression and role of MEKK3 in renal clear cell carcinoma.

To explore the relationship between Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3(MEKK3) and cell apoptosis, clinicopathology, and prognosis, we characterize the expression of MEKK3, survivin and stat3 in renal clear cell carcinoma (RCCC). The expressions were measured by RT-PCR and Western blot from 15 cases of RCCC and 15 cases of control group (CG). Protein expression was detected by tissue microarray and immunochemistry in 98 cases of RCCC, 28 cases of CG. Expression patterns were analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, survivin and stat3 mRNA was significantly higher in RCCC than in CG (P < 0.01). MEKK3, survivin and stat3 expression differed significantly between pathological grade (P < 0.05) and clinical stage (P < 0.05). MEKK3 expression was positively correlated with survivin and stat3 (P < 0.01). Furthermore, we investigated the role of MEKK3 in RCCC using the technique of RNA silencing via small interfering (siRNA) in ACHN cells. The results indicated that the targeted depletion of MEKK3 caused a dramatic massive apoptotic cell death. Kaplan-Meier survival analysis showed that MEKK3 and survivin expression, pathological grade, and clinical stage reduced cumulative survival. Cox multivariate regression analysis showed that MEKK3, survivin, and clinical staging were independent prognostic factors in renal cancer (P < 0.05). MEKK3 can be used as an important marker of prognostic evaluation in RCCC. The mechanism may be closely related to cell apoptosis. Targeted therapy of MEKK3 may provide a new strategy for treatment of chemotherapeutic-resistant tumors.