Growth arrest and DNA-damage-inducible 45 beta (GADD45 beta) deletion suppresses testosterone-induced prostate hyperplasia in mice

Aim: Growth arrest and DNA-damage-inducible 45 beta (GADD45 beta) is a member of the gene family associated with cell growth control, apoptosis, and DNA damage repair. The aim of present study was to determine the potential effects of GADD45 beta deletion on prostate hyperplasia progression. Main methods: LNCaP cells were incubated with testosterone propionate (1 mu M) for 48 h and specific siRNA used to suppress GADD45 beta expression in vitro. For in vivo experiments, testosterone (3 mg/kg, IP) was injected into wild-type (WT) and GADD45 beta knockout (GADD45 beta(-/-)) C57BL/6J mice for 21 consecutive days, and serum and prostate tissues subjected to biological and histochemical analyses. Key findings: GADD45 beta-silenced LNCaP cells showed suppressed testosterone-induced 5 alpha-reductase 2 and androgen receptor expression compared to control LNCaP cells. Moreover, after 21 days of testosterone treatment, prostate weight and stromal tissue increment were relatively lower in GADD45 beta(-/-) than WT counterpart mice. Inhibition of testosterone-induced 5 alpha-reductase 2 and proliferating cell nuclear antigen expression in the GADD45 beta(-/-) group was confirmed via immunohistochemistry analyses. Significance: Although the exact correlation between GADD45 beta and prostate hyperplasia remains to be established, the present GADD45 beta deletion suppressed testosterone-induced prostate hyperplasia which was accompanied by inhibition of 5 alpha-reductase 2-related protein expression.