EXPRESSION OF MN-SUPEROXIDE DISMUTASE IN CARCINOGENESIS

Human liver manganese superoxide dismutase (Mn-SOD) was highly purifie d by a simple procedure and crystallized. A monoclonal antibody agains t Mn-SOD, whose antigen-binding epitope is a C-terminus peptide was de veloped. Using this antibody, an enzyme-linked immunosorbent assay (EL ISA) was developed. We found that Mn-SOD is highly expressed in human ovarian cancer and the serum level of the enzyme is a useful marker fo r the diagnosis and monitoring of the epithelial type of ovarian cance r. Tumor necrosis factor-alpha (TNF), lipopolysaccharide, IL-1 and pho rbol ester induced the m-RNA of Mn-SOD as well as protein levels in TN F-resistant cells. No such induction was observed in Cu, Zn-SOD. Studi es on the induction mechanisms indicated that at least two separate si gnal-transducing pathways are involved in expression of the Mn-SOD gen e. One is triggered by protein kinase C activation itself in the absen ce of new protein synthesis. The other can be activated by stimulation s with various cytokines in which a protein factor that can be induced by phorbol ester treatments is involved.