Glutamate-cysteine ligase catalytic subunit (GCLC) has been reported to overexpress in a variety types of cancer and be related with tumor progression and drug resistance.
Nuclear factor erythroid 2-related factor 2 (NRF2) activates expression of cytoprotective proteins such as GCLC and enhances cancer cell survival, whereas KEAP1 inhibits NRF2 by mediating NRF2 degradation.
GCS levels were analyzed using cancer profiling arrays, breast cancer histo-arrays and quantitative RT-PCR in tumor tissues.We found that breast (18 exp. index) and other hormone-dependent organs (testis, cervix, ovary, prostate) displayed the lowest levels of GCS mRNA, whereas liver (52 exp. index) and other organs (kidney, bladder, stomach) displayed the highest levels of GCS.
Multidrug resistance in cancer cells is often associated with an elevation in the concentration of glutathione (GSH) and the expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for GSH.
Genes encoding both MRP1 and the catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCS) are coordinately regulated in cultured cancer cell lines as well as colorectal cancer tissues from colon cancer patients.