The Enzyme MnSOD Suppresses Malignant Breast Cell Growth by Preventing HIF-1 Activation
Abstract
Hypoxia-inducible factor-l (HIF-l) is an important transcriptional factor that is activated in conditions of decreased oxygen. It mediates cell survival in hypoxia by promoting genes involved in glucose homeostasis, erythropoiesis, and angiogenesis.. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzymes involved in cancer cell growth. Our group has shown both in vitro and in vivo that both tumor growth and vascularization are suppressed with increased MnSOD. We hypothesize that the SOD enzymes and HIF-l are linked and that SOD overexpression in malignant tumors can modulate HIF-l alpha protein levels. To test this hypothesis we exposed MnSOD overexpressing cells to hypoxia and examined HIF-l alpha protein. Our results demonstrated that increase of MnSOD (3-30 fold activity) in breast cancer cells suppressed the accumulation of HIF-l alpha protein under hypoxia in a dose dependent manner. These results suggest that MnSOD regulates HIP-l alpha and that the modulation of HIP-l alpha protein levels may account for the tumor suppressor function of SOD enzyme.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA418673
Entities
People
- Garry Beuttner
- Min Wang
Organizations
- University of Iowa