Tumor necrosis factor is necessary, but not sufficient, for castration induced prostate regression

Abstract

Tumor necrosis factor (TNF) is a pro‐inflammatory cytokine that plays a vital role in immune responses. TNF is also a potent apoptotic stimulus in vitro. However, few reports have demonstrated a physiologic role for TNF induced apoptosis in vivo. Employing high field MRI (magnetic resonance imaging) to measure mouse prostate volume, we demonstrate that the extent of castration induced prostate regression is significantly reduced in mice null for either the TNF or TNFR1 genes. Wild type (WT) mice receiving soluble TNFR2 prior to castration exhibit a nearly identical reduction of prostate regression. Additionally, membrane‐bound TNF protein and TNF mRNA levels increase in the ventral lobe of rat prostate following castration. When injected into the peritoneum of TNF−/− mice at the time of castration, soluble TNF is able to restore normal levels of prostate regression. However, WT mice receiving soluble TNF in the absence of castration do not exhibit prostate regression, indicating that TNF alone is not sufficient, but must act in the context of additional castration induced signals. These findings support a physiologic role for TNF in prostate regression following androgen withdrawal. Understanding this role may lead to novel therapies for prostate cancer.J.S. Davis is supported by DOD Pre‐doctoral Training Grant #PC073208.