Abstract Transforming growth factor-beta3 (TGF-β3) is a member of a family of multifunctional cytokines that control different cellular processes including cell proliferation, morphogenesis, migration, extracellular matrix production, cytokine secretion, and apoptosis, as well as in normal physiological and disease processes. Among the various isoforms of TGF-β, TGF-β1 has been the most studied form, especially in the context of tumor development. In contrast, only few studies have been focused on the role of TGF-β3 in tumorogenesis. Recently, it has been shown that the transcription factors Yin Yang 1 (YY1) is involved in the TGF-β3 pathway. YY1 is known to be associated with cancer progression. One the potential mechanisms of this association is linked with the inactivation of p53. On this ground, the aims of this study were i) to explore the correlated expression of p53 and YY1 in a human benign prostate hyperplasia cell line (BPH-1) and in two prostate cancer cell lines, LNCaP (androgen-sensitive) and DU-145 (androgen-refractory) after treatment with different dose of TGF-β3; ii) to determine, in TGF-β3-treated prostate cell lines, the expression of a fraction of intracellular signalling pathways involved in both cell cycle progression and in apoptosis. TGF-β3 stimulation in prostate cancer cell lines showed different effects, such as YYI downregulation and p53 overexpression. These effects are also associated with a different modulation of intracellular signaling pathways (PI3K, AKT, pAKT, PTEN, Bcl-2, Bax, and iNOS). In conclusion, these findings may have important therapeutic implications in prostate cancer. Citation Format: Silvia Caggia, Saverio Candido, Massimo Libra, Venera Cardile. Transcription factors involved in the genesis and progression of cancer differently modulated by transforming growth factor-beta3 (TGF-Beta3) in prostate cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4074. doi:10.1158/1538-7445.AM2013-4074