Abstract 5569: p73 dinucleotide polymorphism genotyping of human cancer cell lines

Abstract

Abstract The p73 gene is a member of the p53 tumor suppressor family. The p73 dinucleotide polymorphism (DNP) (rs1801173) is a G4C14-to-A4T14 linked pair of transitions located in exon 2 between the P1 and P2 gene promoters. The P1 and P2 p73 gene promoters are the transcription initiation sites for mRNAs encoding TAp73 and ΔNp73 isoforms, respectively. Recently, we reported the p73 DNP allele was associated with (1) decreased risk [OR = 0.55, 95%CI = 0.31-0.99] for aggressive prostate cancer (PCa) and (2) increased TAp73/ΔNp73 protein isoform ratios in ten human cancer cell lines. We hypothesize the presence of the p73 DNP allele causes altered p73 promoter usage resulting in increased TAp73/ΔNp73 protein isoform ratios, which could explain the observed decreased risk for PCa aggressiveness. Our ultimate goal is to assess the potential of p73 DNP as a biomarker for lower aggressive PCa risk. Therefore, our initial aim in this study was to determine the p73 DNP genotype in ten additional human cancer cell lines (DU 145, JEG-3, K-562, LNCaP, MDA-MB-231, MDA-MB-468, MRC-5, PC-3, SW48 and U-2OS) not yet characterized for p73 DNP status. We previously reported the p73 DNP genotype of three human cancer cell lines that we used as genotyping controls: Caco-2 (homozygous polymorphic), NCI-H1299 (homozygous wild type), and HepG2 (heterozygous). Cell lines were cultured and genomic DNA was isolated and quantitated. Cell line genomic DNA samples were used in TaqMan Real Time-PCR allelic discrimination assays to determine the p73 DNP genotypes. Our data conclusively determined that DU 145, JEG-3, K-562, LNCaP, MDA-MB-468, MRC-5, SW48 and U-2OS were p73 DNP homozygous wild type, while PC-3 and MDA-MB-231 werw p73 DNP heterozygous. Cell Line p73 DNP GenotypesCELL LINE NAMEP73 DNP GENOTYPEDU145CCJEG-3CCK-562CCLNCaPCCMDA-MB-231CTMDA-MB-468CCMRC-5CCPC-3CTSW48CCU-2OSCC Citation Format: L. Michael Carastro, Kaia K. Hampton, Ricardo A. Cordova Estupinan, Hyun Y. Park, Dongwha Kim, Jong Y. Park. p73 dinucleotide polymorphism genotyping of human cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5569. doi:10.1158/1538-7445.AM2015-5569