Altered glutamate cysteine ligase expression and activity in renal cell carcinoma.

Abstract

Oxidative stress has been linked to the progression of mutations and cancer. Increased glutathione (GSH) contents have been observed in a number of different human cancer tissues. GSH is synthesized de novo in a two-step process catalyzed by glutamate cysteine ligase (GCL). The present study aimed to investigate whether GCL was associated with renal cell carcinoma (RCC). The protein expression levels of the GCL subunits (catalytic subunit, GCLc; and modulatory subunit, GCLm) and GCL activity were examined in renal cancer tissue. A total of 46 patients fulfilling the RCC criteria of the World Health Organization, revised in 2004, were enrolled. The tumor and adjacent tissues were sampled from all the subjects by surgery. The study demonstrated that GCLc and GCLm protein expression and the GCL activity were significantly increased in the tumor tissue from RCC patients. These results indicate that increased expression and enzymatic activity of GCL is closely associated with RCC and thus, this suggests an important role for GSH in the pathogenesis of RCC.