Cancer-testis (CT) antigen genes display a highly tissue-restricted expression profile; the genes encoding CT antigens are normally expressed in the testes of adult males, but are aberrantly expressed in various types of cancer. The testes confer a site of immune privilege therefore CT antigens represent attractive and potentially important therapeutic and/or diagnostic targets. Sexual reproduction in eukaryotes requires the creation of haploid gametes via a specialised process called meiosis. Meiosis is restricted to germ cells and several meiotic proteins have previously been identified as CT antigens, therefore we hypothesised that meiosis-specific genes may provide a good source from which to identify
novel CT genes.
Meiotic genes were identified from the literature and a bioinformatics pipeline. RT-PCR was used to validate the meiotic genes in a wide range of normal human tissues and those genes found to display testis-associated expression profiles in the normal tissues were screened for expression in a range of cancer cells. The RT-PCR results identified five genes as novel CT genes, out of the 37 genes screened. Biochemical analysis was also carried out on the product of NUT, a novel meiCT gene identified by the CT gene screen.
Surprisingly a significant portion of the purported meiosis-specific genes displayed expression in a wide range of normal human tissues, including RECB and STAG3. The meiosis-specificity of RECS, and its orthologues, has been reported to be widely conserved from yeast to humans. Biochemical analysis results showed that REC8 appears to localise to the nucleus of five human cancer cell lines and fibroblast cells. Here we present evidence to suggest that REC8 displays strong chromatin association in mitotically dividing cells and is
involved in a large protein complex. However, REC8 knockdown in cancer cell lines was unsuccessful and therefore a potential functional role for REC8 could not be established in human mitotic cells.
The results from this study identified five of the meiotic genes as novel CT genes thus supporting the original hypothesis. They also provide evidence to suggest that there are greater differences, than previously proposed, in the control and regulation of meiotic genes and/or proteins within different species.