Oxidative stress defines an imbalance of pro- and anti-oxidants resulting in macromolecular damage as well as disruption of redox signaling and control.

Within the cell, mitochondria are the most critical site of reactive oxygen species (ROS) production. During the process of oxidative phosphorylation mitochondria release 0.4–4% of the consumed oxygen as ROS. To cope with this oxidative burst mitochondria possess different redox regulating systems. The Thioredoxin-dependent system is one of those and includes mitochondrial Thioredoxin (Trx-2), mitochondrial Thioredoxin Reductase (TrxR-2) and peroxiredoxin 3 (Prx3).

Since ROS are known to contribute to malignant events and some types of tumors (e.g. hepatocellular carcinomas) show overexpression of TrxR-2, we are interested in the impact of TrxR-2 on tumor formation and progression.

Therefore we isolated mouse embryonic fibroblasts (MEFs) from TrxR-2 knockout embryos at E12.5. Fibroblasts were transformed with the two protooncogenes c-myc and ha-ras to analyze tumor growth in vitro (soft agar assay) as well as in vivo tumor models.

Interestingly, TrxR-2 deficiency exerts a strong impact on colony growth as well as on tumor progression. Transformed TrxR-2 knockout fibroblasts showed 90% reduced colony growth compared to wildtype cells. Tumors derived from TrxR-2 knockout fibroblasts revealed 50% reduction in tumor size. In addition immunohistological analysis demonstrated a massive decrease of tumor cell proliferation in knockout cell derived tumors.

Further in vivo and in vitro assays will be performed to study the mechanisms of how TRxR-2 blocks tumor growth.