Expression of heavy subunit of γ‐glutamylcysteine synthetase (γ‐GCSh) in human colorectal carcinoma

Gamma‐glutamylcysteine synthetase (γ‐GCS) is a heterodimer consisting of heavy (γ‐GCSh) and light (γ‐GCSl) subunits. γ‐GCS catalyzes the rate‐limiting de novo biosynthesis of glutathione (GSH), an abundant physiological antioxidant that plays important roles for regulating oxidative stress. Expression of γ‐GCSh and γ‐GCSl are sensitive to oxidative stress. To investigate whether expression of γ‐GCS is correlated with tumor progression, we used immunohistochemical approaches to examine 16 human colorectal adenomas and resected 57 carcinomas from untreated patients. In adjacent normal colorectal epithelium, levels of γ‐GCSh expression were low. Strong cytoplasmic staining for γ‐GCSh was detected in 3 (18.8%) adenoma and 48 (84.2%) carcinomas. The frequency of γ‐GCSh expression in carcinoma was significantly higher than in adenoma (p