The putative tumour modifier gene ATP5A1 is not mutated in human colorectal cancer cell lines but expression levels correlate with TP53 mutations and chromosomal instability

<jats:sec> <jats:title>Background:</jats:title> <jats:p>Both the putative modifier gene ATP5a1 and the tumour suppressor gene TP53 are involved in the regulation of apoptosis and may be involved in the development of colorectal cancers.</jats:p> </jats:sec> <jats:sec> <jats:title>Aims:</jats:title> <jats:p>To investigate the relationship between these genes in 16 colorectal cancer cell lines.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Each gene was screened for mutation using high resolution melting analysis and sequencing. Expression of ATP5a1 mRNA was tested by quantitative PCR.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Sequence changes in ATP5a1 were found in 9/16 (56%) cell lines and consisted of mainly novel single nucleotide polymorphisms (SNPs) found in the 5′ UTR, introns 4/5/9 and exon 7. TP53 mutations were also found in 9/16 (56%) cell lines; these were consistent with previous reports. High levels of ATP5a1 expression were seen in cell lines with TP53 mutation compared with those with wild type TP53 (p = 0.02). Furthermore, an A→G change at the −18 position in intron 4 of ATP5a1 was significantly associated with increased gene expression (p = 0.0391). Comparison with genotype showed that cell lines with chromosomal instability (CIN) had significantly higher levels of ATP5a1 expression than those with microsatellite instability (MSI) (p = 0.02).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p> Higher levels of ATP5a1 expression are associated with certain SNPs and with <jats:italic>TP53</jats:italic> mutation. High expression also occurs in CIN and may facilitate tumour development along this pathway. Conversely, low levels of ATP5a1 expression may facilitate development of tumours with MSI. </jats:p> </jats:sec>