TRAF6 Regulates Proliferation Of Stromal Cells In The Transition And Peripheral Zones Of Benign Prostatic Hyperplasia

Objective: To analysis the role of tumor necrosis factor receptorassociated factor 6(TRAF6)in benign prostatic hyperplasia(BPH)stromal cells,and to study the potential mechanisms of stromal TRAF6 in promoting BPH progression.Methods: Specimens of benign prostate hyperplasia were collected by radical cystoectomy from male patients,and according to the McNeal's location cut tissues from TZ and PZ of the prostste.The expression of TRAF6 in stromal cells from different zones were identified by immunohistochemical analysis(IHC)and quantitative real-time PCR(Q-PCR).Stromal cells obtained from BPH-derived primary cultures,and the cells had been immortalized.The TRAF6-siRNA vector were constructed and transfected into cultured human BPH primary TZ stromal cells,and TRAF6-overexpressing vector were constructed and transfected into cultured human BPH primary PZ stromal cells.Stromal cells were recombined with BPH-1 cells then subcutaneously inoculated into the kidney capsule of male nude mice.Cell proliferation was evaluated by CCK-8 assay.Multiple proteins in the Akt/mTOR pathway were assessed using western blot.Results: TRAF6 levels were increased in TZ stroma compared with PZ stroma of BPH.The in vitro cell culture and in vivo cell recombination revealed that selective downregulation of TRAF6 in TZ stromal cells led to suppression of the proliferation,while upregulation of TRAF6 in PZ stromal cells enhanced the proliferation.We found that the Phosphorylation and Ubiquitination of Akt as well as the Phosphorylation of mTOR,P70S6 K were decreased when TRAF6 was downregulated in primary cultured TZ stromal cells of BPH,while the Phosphorylation and Ubiquitination of Akt as well as the Phosphorylation of mTOR,P70S6 K were increased when TRAF6 was upregulated in primary cultured PZ stromal cells of BPH.Conclusions: There are differences of expression of TRAF6 between stromal cells from TZ and PZ of BPH.TRAF6 can promote the proliferation of stromal cells of BPH via Akt/mTOR signaling.Our results may make stromal TRAF6 responsible for zonal characteristic of BPH and as a promising therapeutic strategy for BPH treatment.