Alterations in p53 Influence hTERT, VEGF and MMPs Expression in Oral Cancer Patients.

Abstract

Mutant p53 is the crucial molecule in the etiopathogenesis of oral cancer. Therefore, we aimed to evaluate the impact of alterations of the p53 gene and its negative feedback regulator, MDM2, on the expression of hTERT, VEGF, and MMPs; the critical genes involved in oral cancer progression. p53 and MDM2 genotyping were done by PCR-RFLP. p53 mutation analysis was performed using PCR-SSCP and sequencing. hTERT, VEGFA isoforms, MMP2, and MMP9 mRNA levels were analyzed by semi-quantitative Reverse Transcriptase PCR. Arg allele at p53 exon 4 was significantly associated with overexpression of hTERT, MMP2, and MMP9 individually. Expression of hTERT, VEGF A isoforms, MMP2 and MMP9 were significantly altered in the presence of p53 and MDM2 polymorphisms and p53 mutations in a specific combination. Mutant p53, Arg allele at p53 exon 4 locus, and G/G/or T/T genotype at MDM2revealed increased expression of hTERT, VEGF A isoforms, and MMP2/9. This study provides evidence that apart from mutant p53, naturally occurring sequence variants in p53codon 72 (Arg72Pro) (rs1042522) and MDM2 (rs2279744) significantly alter the expression of hTERT, VEGF-A isoforms, and MMP2/9 in a specific combination. The differential interaction of codon 72 variants with MDM2, hTERT, VEGF-A isoforms and MMP2/9 play a role in the aggressiveness of oral cancer. The results have important implications for oral cancer progression and should be explored for innovative treatment options.