Growth arrest and DNA-damage-inducible 45 beta (GADD45β) deletion suppresses testosterone-induced prostate hyperplasia in mice

Publication date: Available online 6 September 2018Source: Life SciencesAuthor(s): Se-Ra Park, Da-Young Jung, Tae-Won Kim, Chul-Ho Lee, Ju-Young JungAbstractAimGrowth arrest and DNA-damage-inducible 45 beta (GADD45β) 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 GADD45β deletion on prostate hyperplasia progression.Main methodsLNCaP cells were incubated with testosterone propionate (1 μM) for 48 h and specific siRNA used to suppress GADD45β expression in vitro. For in vivo experiments, testosterone (3 mg/kg, IP) was injected into wild-type (WT) and GADD45β knockout (GADD45β−/−) C57BL/6J mice for 21 consecutive days, and serum and prostate tissues subjected to biological and histochemical analyses.Key findingsGADD45β-silenced LNCaP cells showed suppressed testosterone-induced 5α-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 GADD45β−/− than WT counterpart mice. Inhibition of testosterone-induced 5α-reductase 2 and proliferating cell nuclear antigen expression in the GADD45β−/− group was confirmed via immunohistochemistry analyses.SignificanceAlthough the exact correlation between GADD45β and prostate hyperplasia remains to be established, the present GADD45βdeletion suppresse...
Source: Life Sciences - Category: Biology Source Type: research