Abstract Prostate cancer (PCa) is the most common malignancy among men in the USA. Polyphenon E (PolyE) is a standardized blend of polyphenols found in green tea extract, which has been shown to have chemoprevention value in PCa models, but the molecular mechanism(s) have not been elucidated. The p73 gene is a member of the p53 tumor suppressor family. A p73 dinucleotide polymorphism (DNP) (rs1801173) is a G4C14-to-A4T14 linked pair of transitions located in exon 2 and lies between the P1 and P2 gene promoters. The P1 and P2 p73 gene promoters are the transcription initiation sites for mRNAs encoding TAp73 and deltaNp73 (DNp73) isoforms, respectively. These p73 mRNA isoforms, TAp73 and áNp73, encode protein isoforms which differ in their N-termini. TAp73 isoforms include the full-length N-terminal sequence and are transcriptionally active. áNp73 isoforms lack the N-terminal trans-activation domain and are dominate negative. Recently, we reported the p73 DNP allele was associated with (1) decreased risk [OR = 0.55, 95%CI = 0.31-0.99] for aggressive PCa and (2) increased TAp73/DNp73 protein isoform ratios in ten human cancer cell lines. We hypothesize that exposure to PolyE induces changes in TAp73/DNp73 mRNA isoform ratios. Our goal for this study is to assess the effect of PolyE on total p73 mRNA levels and TAp73/DNp73 mRNA isoform ratios using two human PCa cell lines with different p73 DNP genotypes: DU145 (wild-type) and PC-3 (heterozygous). Cultured cells were treated with PolyE (100 or 200 mg/L). Cellular RNA was isolated, converted to cDNA and used in TaqMan RT-PCR assays to detect total p73, TAp73 or DNp73 isoform mRNAs. Our data from PolyE treatments of both DU145 and PC-3 cells are consistent with increased p73 mRNA levels (2.05 and 1.60 fold, respectively) and higher TAp73/DNp73 mRNA ratios (1.13 and 1.29 fold, respectively) at the low Poly E level (100 mg/L). At the high PolyE level (200 mg/L), the TAp73/DNp73 mRNA ratios significantly decreased for both DU145 and PC-3 (0.54 and 0.49 respectively). However, the overall p73 mRNA levels was not changed in DU145 (0.91 fold), but increased in PC-3 (1.60 fold) as compared with level in negative control at the high Poly E concentration. Therefore, in this exploratory study, PolyE treatment of the two PCa cell lines tested using a more moderate concentration of 100 mg/L results in higher overall p73 levels and increased TAp73/DNp73 mRNA ratios. This data could provide a potential molecular rationale for the observation that Poly E treatments provide chemopreventative impact against PCa. Citation Format: L. Michael Carastro, Ricardo A. Cordova, Christopher D. Cole, Jong Y. Park. Polyphenon E treatment affects p73 mRNA levels. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 827.