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

The melanoma antigen (MAGE) genes were initially isolated from melanomas and turned out to have an almost exclusively tumor-specific expression pattern. This led to the idea of using MAGE genes as targets for cancer immunotherapy, and MAGE peptides are currently being investigated as immunizing agents in clinical studies. Although 23 human and 12 mouse MAGE genes have been isolated in various tumors and characterized, not much is known about their function in normal cells. In adult tissues, most MAGE genes are expressed only in the testis and expression patterns suggest that this gene family is involved in germ cell development. In contrast to the MAGE genes, more functional data have accumulated around the MAGE related gene necdin. This gene encodes a neuron-specific growth suppressor that facilitates the entry of the cell into cell cycle arrest. Necdin is functionally similar to the retinoblastoma protein and binds to and represses the activity of cell-cycle-promoting proteins such as SV40 large T, adenovirus E1A, and the transcription factor E2F. Necdin also interacts with p53 and works in an additive manner to inhibit cell growth. In this review we will focus on the normal functions of MAGE genes and we speculate, based on the patterns of MAGE expression and on observed functions of necdin, that this gene family is involved in cell cycle regulation, especially during germ cell development.