MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than inin situcarcinomas or non-neoplastic breast epithelial cells

Abstract

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme capable of neutralizing superoxide anion molecules. In previous studies it has been suggested to suppress both tumour proliferation and apoptosis. This study investigated 65 invasive, 50 in situ and 19 benign hyperplastic breast lesions for its immunohistochemical expression. MnSOD expression was also tested with in situ hybridization. To study cell proliferation, apoptosis and their association with MnSOD expression the neoplastic breast lesions were immunostained with a monoclonal antibody to Ki-67 and the extent of apoptosis in them was determined by the TUNEL method. 32/65 (49%) of the invasive ductal carcinomas, 41/50 (82%) of the in situ and 15/19 (79%) of the benign hyperplasias expressed the MnSOD protein. There were significantly more MnSOD positive cases in in situ carcinoma and in benign hyperplasia than in invasive carcinoma (p=0.00016 and p=0.022, respectively). Positivity was also more frequently found in non-neoplastic ductal and acinar epithelial cells than in invasive carcinoma. On the other hand, neoplastic epithelial cells of invasive and in situ carcinoma showed strong positivity more often than the epithelial cells of benign hyperplasia or non-neoplastic epithelium. In breast lesions, MnSOD positivity did not associate with proliferation or apoptosis. The lower frequency of MnSOD positive cases in invasive breast carcinoma suggests that the lack of its expression might contribute to the development of an invasive breast carcinoma phenotype and that it could in this way operate as a tumour suppressor gene, as previously suggested.

Different Association of Manganese Superoxide Dismutase Gene Polymorphisms with Risk of Prostate, Esophageal, and Lung Cancers: Evidence from a Meta-analysis of 20,025 Subjects

“…Molecularly, the MnSOD Ala/Ala genotype causes an amino acid substitution from valine (Val) to alanine (Ala),which reduces MnSOD enzymatic activity and its ability to remove ROS (Sutton et al, 2003). The latter was confirmed to play an important role in regulating cell proliferation and carcinogenesis (Soini et al, 2001). Studies on human tissue specimens showed that MnSOD was absent or reduced in breast cancer (Soini et al, 2001) and prostate cancer (Wang et al, 2006).…”

Epigenetic Regulation of Manganese Superoxide Dismutase Expression in Human Breast Cancer Cells

“…Previous studies have shown that MnSOD expression is down regulated in breast carcinoma cells compared to their normal cells of origin. 3 To query the molecular mechanism(s) for differential MnSOD expression in normal versus tumor we used the breast carcinoma cell line MDA-MB-435 and the immortalized breast epithelial line MCF-10A. First, we used quantitative real time RT-PCR to compare the levels of SOD2 transcript in these cell lines (Fig.…”

“…MnSOD expression is altered in primary breast tumors compared to the tissues from which they arise. 3 Our study has identified one region of the SOD2 promoter that can be analyzed to compare CpG methylation between primary breast tumor samples and isogenic normal breast epithelial cells. Such studies are currently being undertaken in our laboratory to further elucidate the role epigenetic regulation of SOD2 plays in human breast cancer.…”

“…8 Breast carcinoma cells and primary tumors generally have lower MnSOD expression and activity than their normal nontumorgenic counterparts. 3 However, the precise mechanism leading to the down regulation of MnSOD during malignant transformation is unclear.…”

“…MnSOD works in concert with other antioxidant enzymes to protect cells from the damage associated with exposure to reactive oxygen species (ROS). Several reports indicate that MnSOD mRNA, protein, and activity are decreased in many types of human primary tumors [1][2][3] (reviewed in ref. 4).…”