Mechanism of DNA Polymerase Beta Hyper-expression in Malignant Transformation Induced by Benzo[a] Pyrene
Abstract
Objective To explore the mechanism of the hyper-expression of DNA polymerase beta (polβ) in benzo[a]pyrene (BaP) induced malignant transformed cell (polβ-T). Methods The mutation of polβ gene exon and promoter were examined using reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) and gene sequencing. The expression of protein-arginine N-methyhransferase 6 (PRMT6) mRNA and protein in polβ-T cell and control cell (polβ cell) were investigated by RT-PCR and Western blot. Results RT-PCR-SSCP and gene sequencing revealed that the hyper-expression of polβ in polβ-T cell was not associated with the mutation of polβ gene exon while insert mutation (G) and point mutation (C→A) were found located in the core region of polβ gene promoter. Furthermore, the expression of PRMT6 mRNA and protein also increased in polβ-T cell compared with control cell (P<0.05). Conclusion The enhancement of expression of polβ in polβ-T cell might be attributed to the mutations locating in polβ gene promoter on transcription level of polβ gene, and PRMT6 might also enhance the expression of polβ in polβ-T cell through relative epigenetic pathways.
Keywords: Benzo[a]pyrene Cell transformation, neoplastic Protein-arginine N-methyhransferase 6 DNA polymerase beta
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