Recent research studies have established a link between a common type of breast cancer in older women and a protein that fends off aging-related cellular damage.
The study, led by Vanderbilt-Ingram Cancer Center researcher David Gius, has shown how deficiency in this aging-associated protein may set the stage for estrogen and progesterone receptor (ER/PR) positive breast cancer to develop.
The findings have provided information that could assist in the screening, prevention and treatment of these common age-related cancers.
But how deficiency in a longevity gene led to increased ROS was not clear.
Since superoxide is generally removed from the cell with the help of a detoxifying enzyme called manganese superoxide dismutase (MnSOD), Gius hypothesized that the Sirt3 deficiency may abnormally regulate MnSOD.
In the current study, the researchers show that Sirt3 knockout mice have decreased MnSOD activity despite having normal levels of the protein.
Gius and colleagues determined that the MnSOD in Sirt3 knockout mice was abnormally modified (with a chemical "acetyl" group) at a specific amino acid (lysine 122).
This aberrant modification of MnSOD reduced the enzyme's ability to detoxify superoxide and appeared to explain the increase in ROS in Sirt3 knockout mouse tumors.
"These results suggest that aberrant regulation of MnSOD plays a role in receptor positive breast cancer," said Gius.
The findings were published in Molecular Cell.