It is known that HER2/neu upregulations are associated with many human cancers and approximately 30% in breast cancer patients. Therefore, HER2/neu is a useful target for developing anticancer drugs. Overexpression of human manganese-containing superoxide dismutase (MnSOD) activity has been demonstrated to suppress many carcinoma cells, including the breast carcinoma, in vitro and in vivo. We found for the first time that the MnSOD suppresses the HER2/neu oncogene expression at the transcriptional level. To further unravel its effects on HER2/neu-overexpressing breast cancer cells, stable transfection and overexpression of MnSOD in HER2/neu-overexpressing breast cancer MDA-MB-453 cells were conducted. The MnSOD-overexpressing cell clones were found to be able to down-regulate the endogenous production of p185HER2/neu. In addition, the MnSOD-overexpressing stable transfectants showed reduced low soft agarose colony forming ability and metastatic properties as compared with the wild-type parental- or vector control-transfected cell clones. These data suggest that MnSOD may be used to treat human breast tumor malignancy mediated by HER2/neu oncogene.
