Transcription factors involved in the genesis and progression of cancer differently modulated by transforming growth factor-beta3 (TGF-beta3) in prostate cell lines

Abstract

Transforming growth factor-beta (TGF-beta) 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. TGF-beta utilizes a multitude of intracellular signaling pathways in addition to Smads with actions that are dependent on circumstances, including dose, target cell type, and context. TGF-beta pathway has been implicated in cancer and has been recently considered as a putative therapeutic target. The aims of this study were to verify the effects of dose-dependent TGF-beta3 treatment in BPH-1 cell line, human benign prostate hyperplasia, and two prostate cancer cell lines, LNCaP, which is androgen-sensitive, and DU-145, which is androgen-non responsive, evaluating a correlation between p53 and YY1. Moreover, the expression of several parameters (PI3K, AKT, pAKT, PTEN, Bcl-2, Bax, PARP, Rb, pRb, cyclin A and iNOS) involved in both cell cycle progression and in apoptosis was evaluated through Western blot analysis on prostate cultures treated with 10 and 50 ng/ml of TGF-beta3 for 24 h. The production of nitric oxide (NO ) was determined by Griess reagent and cell viability by MTT assay. The results of this research demonstrated profound differences in the responses of the BPH-1, LNCaP, and DU- 145 cell lines to TGF-beta3 stimulation. We believe that the findings could be important because of the clinical relevance that they may assume and the therapeutic implications for TGF-beta treatment of prostate cancer.