The mismatch repair gene hPMS1 (human postmeiotic segregation1) is down regulated in oral squamous cell carcinoma

- hPMS1 protein was found to be down regulated in MSI + tumors by IHC and Western blot.
- hPMS1 mRNA expression was not affected by Northern blot analysis.
- No mutation and methylation changes were found in the gene.
- We believed that the down regulated PMS1 is the cause for high MSI in OSCC.
- hPMS1 is most likely deregulated by post-transcriptional modification in OSCC.

Genomic instability or microsatellite instability (MSI) was initially recognized in colonic carcinoma and subsequently in other tumors. MSI has been associated with mutations in genes that play a role in DNA replication and repair. In a previous study we detected MSI in 85% of young patients with OSCC and excluded the involvement of MMR genes hMLH1 and hMSH2. In the present study, we screened the mutation and expression status of the MMR genes hMSH3, hMSH6, hPMS1 and hPMS2 in OSCC and found expression of the hPMS1 protein to be down regulated. Genomic analysis of hPMS1 did not show any mutational changes in exonic or promoter regions. Expression of hPMS1 mRNA was not deregulated in either MSI positive or MSI negative tumor cell lines by Northern blot analysis. In contrast, analysis by Western blot showed that 100% of MSI positive tumor cell lines had decreased or no expression of hPMS1 while MSI negative cell lines had normal protein expression. Our data indicate that hPMS1 is most likely deregulated by post-transcriptional modification in OSCC while hMLH1 and hPMS2 has no detectable changes. Furthermore, our results are consistent with the hypothesis that hPMS1 is associated with MSI in OSCC.