The melanoma antigen genes - Any clues to their functions in normal tissues?

The melanoma antigen (MAGE) genes were initially isolated from melanomas an d turned out to have an almost exclusively tumor-specific expression patter n. This led to the idea of using MAGE genes as targets for cancer immunothe rapy, and MAGE peptides are currently being investigated as immunizing agen ts in clinical studies. Although 23 human and 12 mouse MAGE genes have been isolated in various tumors and characterized, not much is known about thei r function in normal cells. In adult tissues, most MAGE genes are expressed only in the testis and expression patterns suggest that this gene family i s involved in germ cell development. In contrast to the MAGE genes, more fu nctional data have accumulated around the MAGE related gene necdin. This ge ne encodes a neuron-specific growth suppressor that facilitates the entry o f the cell into cell cycle arrest. Necdin is functionally similar to the re tinoblastoma protein and binds to and represses the activity of cell-cycle- promoting proteins such as SV40 large T, adenovirus E1A, and the transcript ion factor E2F. Necdin also interacts with p53 and works in an additive man ner to inhibit cell growth. In this review me will focus on the normal func tions of MAGE genes and me speculate, based on the patterns of MAGE express ion and on observed functions of necdin, that this gene family is involved in cell cycle regulation, especially during germ cell development. (C) 2001 Academic Press.